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Immune-Checkpoint Inhibitors: A New Line of Attack in Triple-Negative Breast Cancer

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Breast Cancer Research and Treatment

Part of the book series: Cancer Treatment and Research ((CTAR,volume 188))

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Abstract

Poor prognosis is a distinctive feature of triple-negative breast cancer (TNBC). Chemotherapy has long represented the main and unique treatment for patients with TNBC. Recently, immune checkpoint inhibitors (ICIs) were investigated in several clinical trials and were approved for clinical use in TNBC patients that express programmed cell death protein-1 (PD-1) in combination with chemotherapy in the first-line setting. ICIs are also being investigated in the neoadjuvant and adjuvant settings for TNBC. This chapter aims to discuss different ICIs used to treat all TNBC stages to date.

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References

  1. Farshbafnadi M, Khoshbin AP, Rezaei N (2021) Immune checkpoint inhibitors for triple-negative breast cancer: from immunological mechanisms to clinical evidence. Int Immunopharmacol 98:107876. https://doi.org/10.1016/j.intimp.2021.107876

  2. Li CH, Karantza V, Aktan G, Lala M (2019) Current treatment landscape for patients with locally recurrent inoperable or metastatic triple-negative breast cancer: a systematic literature review. Breast Cancer Res 21(1):143. https://doi.org/10.1186/s13058-019-1210-4

  3. Cabel L, Carton M, Pistilli B, Dalenc F, Vanlemnens L, Levy C, Jacot W, Debled M, Loeb A, Hennequin A, De la Motte T, Rouge LL, Carine Laurent E, Chamorey DP, Petit T, Mouret-Reynier M-A, Campone M, Perrocheau G, Labreveux C, Bachelot T, Robain M, Lerebours F (2021) Outcome beyond third-line chemotherapy for metastatic triple-negative breast cancer in the French ESME Program. Breast : Off J Eur Soc Mastolog 56:18–25. https://doi.org/10.1016/j.breast.2021.01.006

  4. Schreiber AR, Kagihara JA, Weiss JA, Nicklawsky A, Gao D, Borges VF, Kabos P, Diamond JR (2021) ‘Clinical outcomes for patients with metastatic breast cancer treated with immunotherapy agents in phase I clinical trials’. Frontiers Oncol 11

    Google Scholar 

  5. Vikas P, Borcherding N, Zhang W (2018) The clinical promise of immunotherapy in triple-negative breast cancer. Cancer Manag Res 10:6823–6833. https://doi.org/10.2147/CMAR.S185176

  6. Stanton SE, Adams S, Disis ML (2016) Variation in the incidence and magnitude of tumor-infiltrating lymphocytes in breast cancer subtypes: a systematic review. JAMA Oncol 2(10):1354–1360. https://doi.org/10.1001/jamaoncol.2016.1061

  7. Fan Y, He S (2022) The characteristics of tumor microenvironment in triple negative breast cancer. Cancer Manag Res 14:1–17. https://doi.org/10.2147/CMAR.S316700

  8. Mittendorf EA, Philips AV, Meric-Bernstam F, Qiao N, Wu Y, Harrington S, Su X, Wang Y, Gonzalez-Angulo AM, Akcakanat A, Chawla A, Curran M, Hwu P, Sharma P, Litton JK, Molldrem JJ, Alatrash G (2014) ‘PD-L1 expression in triple-negative breast cancer’. Cancer Immunol Res 2(4):361–370. https://doi.org/10.1158/2326-6066.CIR-13-0127

  9. O’Meara TA, Tolaney SM (2021) Tumor mutational burden as a predictor of immunotherapy response in breast cancer. Oncotarget 12(5):394–400. https://doi.org/10.18632/oncotarget.27877

  10. Oner G, Altintas S, Canturk Z, Tjalma W, Verhoeven Y, Van Berckelaer C, Berneman Z, Peeters M, Pauwels P, van Dam PA (2020) Triple-negative breast cancer—role of immunology: a systemic review. Breast J 26(5):995–999. https://doi.org/10.1111/tbj.13696

  11. Shah SP, Roth A, Goya R, Oloumi A, Ha G, Zhao Y, Turashvili G, Ding J, Tse K, Haffari G, Bashashati A, Prentice LM, Khattra J, Burleigh A, Yap D, Bernard V, McPherson A, Shumansky K, Crisan A, Giuliany R, Heravi-Moussavi A, Rosner J, Lai D, Birol I, Varhol R, Tam A, Dhalla N, Zeng T, Ma K, Chan S, Griffith M, Moradian A, Grace Cheng SW, Morin GB, Watson P, Gelmon K, Chia S, Chin S-F, Curtis C, Rueda O, Pharoah PD, Damaraju S, Mackey J, Hoon K, Harkins T, Tadigotla V, Sigaroudinia M, Gascard P, Tlsty T, Costello JF, Meyer IM, Eaves CJ, Wasserman WW, Jones S, Huntsman D, Hirst M, Caldas C, Marra MA, Aparicio S (2012) ‘The clonal and mutational evolution spectrum of primary triple negative breast cancers’. Nature 486(7403): https://doi.org/10.1038/nature10933

  12. Efremova M, Finotello F, Rieder D, Trajanoski Z (2017) Neoantigens generated by individual mutations and their role in cancer immunity and immunotherapy. Front Immunol 8:1679. https://doi.org/10.3389/fimmu.2017.01679

  13. Pardoll DM (2012) The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer 12(4):252–264. https://doi.org/10.1038/nrc3239

  14. Chien AJ, Gliwa AS, Rahmaputri S, Dittrich HF, Majure MC, Rugo HS, Melisko ME, Munster PN, Park JW, Moasser MM, Matloubian M, Lea T, Rohrberg J, Krings G, Goga A (2020) ‘A phase Ib trial of the cyclin-dependent kinase inhibitor dinaciclib (Dina) in Combination with Pembrolizumab (P) in Patients with Advanced Triple-Negative Breast Cancer (TNBC) and response correlation with myc-overexpression.’ J Clin Oncol 38(15_suppl):1076–1076. https://doi.org/10.1200/JCO.2020.38.15_suppl.1076.

  15. Fujiwara Y, Mittra A, Rafeh Naqash A, Takebe N (2020) ‘A review of mechanisms of resistance to immune checkpoint inhibitors and potential strategies for therapy’. Cancer Drug Resistance 3(3):252–75. https://doi.org/10.20517/cdr.2020.11

  16. Rieth J, Subramanian S (2018) Mechanisms of intrinsic tumor resistance to immunotherapy. Int J Mol Sci 19(5):1340. https://doi.org/10.3390/ijms19051340

  17. Zaretsky JM, Garcia-Diaz A, Shin DS, Escuin-Ordinas H, Hugo W, Hu-Lieskovan S, Torrejon DY, Abril-Rodriguez G, Sandoval S, Barthly L, Saco J, Moreno BH, Mezzadra R, Chmielowski B, Ruchalski K, Shintaku IP, Sanchez PJ, Puig-Saus C, Cherry G, Seja E, Kong X, Pang J, Berent-Maoz B, Comin-Anduix B, Graeber TG, Tumeh PC, Schumacher TNM, Lo RS, Ribas A (2016). ‘Mutations associated with acquired resistance to PD-1 blockade in melanoma’. N Engl J Med 375(9):819–29. https://doi.org/10.1056/NEJMoa1604958

  18. Bai R, Chen N, Li L, Du N, Bai L, Lv Z, Tian H, Cui J (2020) ‘Mechanisms of cancer resistance to immunotherapy’. Frontiers Oncol 10:1290. https://doi.org/10.3389/fonc.2020.01290

  19. Peggs KS, Quezada SA, Chambers CA, Korman AJ, Allison JP (2009) Blockade of CTLA-4 on both effector and regulatory T cell compartments contributes to the antitumor activity of anti–CTLA-4 antibodies. J Exp Med 206(8):1717–1725. https://doi.org/10.1084/jem.20082492

  20. Rudd CE, Taylor A, Schneider H (2009) CD28 and CTLA-4 Coreceptor Expression and Signal Transduction. Immunol Rev 229(1):12–26. https://doi.org/10.1111/j.1600-065X.2009.00770.x

  21. Chemnitz JM, Parry RV, Nichols KE, June CH, Riley JL (2004) ‘SHP-1 and SHP-2 associate with immunoreceptor tyrosine-based switch motif of programmed death 1 upon primary human T cell stimulation, but only receptor ligation prevents T cell activation’. J Immunol (Baltimore, Md.: 1950) 173(2):945–54. https://doi.org/10.4049/jimmunol.173.2.945.

  22. van Kooten C, Banchereau J (2000) CD40-CD40 Ligand. J Leukoc Biol 67(1):2–17. https://doi.org/10.1002/jlb.67.1.2

  23. Byrne KT, Vonderheide RH (2016) CD40 stimulation obviates innate sensors and drives T cell immunity in cancer. Cell Rep 15(12):2719–2732. https://doi.org/10.1016/j.celrep.2016.05.058

  24. Croft M (2010) Control of immunity by the TNFR-related molecule OX40 (CD134). Annu Rev Immunol 28:57–78. https://doi.org/10.1146/annurev-immunol-030409-101243

  25. Curti BD, Kovacsovics-Bankowski M, Morris N, Walker E, Chisholm L, Floyd K, Walker J, Gonzalez I, Meeuwsen T, Fox BA, Moudgil T, Miller W, Haley D, Coffey T, Fisher B, Delanty-Miller L, Rymarchyk N, Kelly T, Crocenzi T, Bernstein E, Sanborn R, Urba WJ, Weinberg AD (2013) ‘OX40 Is a potent immune-stimulating target in late-stage cancer patients’. Cancer Res 73(24):7189–98. https://doi.org/10.1158/0008-5472.CAN-12-4174

  26. Granier C, Dariane C, Combe P, Verkarre V, Urien S, Badoual C, Roussel H, Mandavit M, Ravel P, Sibony M, Biard L, Radulescu C, Vinatier E, Benhamouda N, Peyromaure M, Oudard S, Méjean A, Timsit M-O, Gey A, Tartour E (2017) Tim-3 Expression on tumor-infiltrating PD-1+CD8+ T cells correlates with poor clinical outcome in renal cell carcinoma. Can Res 77(5):1075–1082. https://doi.org/10.1158/0008-5472.CAN-16-0274

  27. Thommen DS, Schreiner J, Müller P, Herzig P, Roller A, Belousov A, Umana P, Pisa P, Klein C, Bacac M, Fischer OS, Moersig W, Prince SS, Levitsky V, Karanikas V, Lardinois D, Zippelius A (2015) Progression of lung cancer is associated with increased dysfunction of T cells defined by coexpression of multiple inhibitory receptors. Cancer Immunol Res 3(12):1344–1355. https://doi.org/10.1158/2326-6066.CIR-15-0097

  28. Solomon BL, Garrido-Laguna I (2018) ‘TIGIT: a novel immunotherapy target moving from bench to bedside’. Cancer Immunol, Immunother CII 67(11):1659–1667. https://doi.org/10.1007/s00262-018-2246-5

  29. Kouo T, Huang L, Pucsek AB, Cao M, Solt S, Armstrong T, Jaffee E (2015) Galectin-3 shapes antitumor immune responses by suppressing CD8+ T Cells via LAG-3 and Inhibiting expansion of plasmacytoid dendritic cells. Cancer Immunol Res 3(4):412–423. https://doi.org/10.1158/2326-6066.CIR-14-0150

  30. Thomas R, Al-Khadairi G, Decock J (2021) ‘Immune Checkpoint inhibitors in triple negative breast cancer treatment: promising future prospects’. Frontiers Oncol 10

    Google Scholar 

  31. Nanda R, Laura QM, Chow EC, Dees RB, Gupta S, Geva R, Pusztai L, Pathiraja K, Aktan G, Cheng JD, Karantza V, Buisseret L (2016) Pembrolizumab in patients with advanced triple-negative breast cancer: phase Ib KEYNOTE-012 study. J Clin Oncol 34(21):2460–2467. https://doi.org/10.1200/JCO.2015.64.8931

  32. Adams S, Loi S, Toppmeyer D, Cescon DW, De Laurentiis M, Nanda R, Winer EP, Mukai H, Tamura K, Armstrong A, Liu MC, Iwata H, Ryvo L, Wimberger P, Rugo HS, Tan AR, Jia L, Ding Y, Karantza V, Schmid P (2019) ‘Pembrolizumab monotherapy for previously untreated, PD-L1-positive, metastatic triple-negative breast cancer: cohort B of the phase II KEYNOTE-086 Study’. Annals Oncol 30(3):405–11. https://doi.org/10.1093/annonc/mdy518

  33. Loi S, Drubay D, Adams S, Pruneri G, Francis PA, Lacroix-Triki M, Joensuu H, Vittoria Dieci M, Badve S, Demaria S, Gray R, Munzone E, Lemonnier J, Sotiriou C, Piccart MJ, Kellokumpu-Lehtinen P-L, Vingiani A, Gray K, Andre F, Denkert C, Salgado R, Michiels S (2019). ‘Tumor-infiltrating lymphocytes and prognosis: a pooled individual patient analysis of early-stage triple-negative breast cancers’. J Clin Oncol 37(7):559–569. https://doi.org/10.1200/JCO.18.01010

  34. Cortes J, Cescon DW, Rugo HS, Nowecki Z, Im S-A, Yusof MM, Gallardo C, Lipatov O, Barrios CH, Holgado E, Iwata H, Masuda N, Otero MT, Gokmen E, Loi S, Guo Z, Zhao J, Aktan G, Karantza V, Schmid P (2020) ‘KEYNOTE-355: Randomized, Double-Blind, Phase III study of Pembrolizumab + Chemotherapy versus Placebo + Chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer.’ J Clin Oncol 38(15_suppl):1000–1000. https://doi.org/10.1200/JCO.2020.38.15_suppl.1000

  35. Cortés J, Lipatov O, Im SA, Gonçalves A, Lee KS, Schmid P, Tamura K, Testa L, Witzel I, Ohtani S, Zambelli S, Harbeck N, André F, Dent R, Zhou X, Karantza V, Mejia JA, Winer EP (2019) LBA21 - KEYNOTE-119: phase III study of pembrolizumab (Pembro) versus single-agent chemotherapy (Chemo) for metastatic triple negative breast cancer (MTNBC). Ann Oncol 30:v859–v860. https://doi.org/10.1093/annonc/mdz394.010

  36. Emens LA, Cruz C, Eder JP, Braiteh F, Chung C, Tolaney SM, Kuter I, Nanda R, Cassier PA, Delord J-P, Gordon MS, ElGabry E, Chang C-W, Sarkar I, Grossman W, O’Hear C, Fassò M, Molinero L, Schmid P (2019) Long-Term clinical outcomes and biomarker analyses of atezolizumab therapy for patients with metastatic triple-negative breast cancer. JAMA Oncol 5(1):74–82. https://doi.org/10.1001/jamaoncol.2018.4224

  37. Dirix LY, Takacs I, Jerusalem G, Nikolinakos P, Arkenau H-T, Forero-Torres A, Boccia R, Lippman ME, Somer R, Smakal M, Emens LA, Hrinczenko B, Edenfield W, Gurtler J, von Heydebreck A, Grote HJ, Chin K, Hamilton EP (2018) ‘Avelumab, an Anti-PD-L1 antibody, in patients with locally advanced or metastatic breast cancer: a phase 1b JAVELIN solid tumor study’. Breast Cancer Res Treat 167(3):671–86. https://doi.org/10.1007/s10549-017-4537-5

  38. Emens LA, Middleton G (2015) The Interplay of immunotherapy and chemotherapy: harnessing potential synergies. Cancer Immunol Res 3(5):436–443. https://doi.org/10.1158/2326-6066.CIR-15-0064

  39. Sistigu A, Yamazaki T, Vacchelli E, Chaba K, Enot DP, Adam J, Vitale I, Goubar A, Baracco EE, Remédios C, Fend L, Hannani D, Aymeric L, Ma Y, Niso-Santano M, Keep O, Schultze JL, Tüting T, Belardelli F, Bracci L, La Sorsa V, Ziccheddu G, Sestili P, Urbani F, Delorenzi M, Lacroix-Triki M, Quidville V, Conforti R, Spano J-P, Pusztai L, Poirier-Colame V, Delaloge S, Penault-Llorca F, Ladoire S, Arnould L, Cyrta J, Dessoliers M-C, Eggermont A, Bianchi ME, Pittet M, Engblom C, Pfirschke C, Préville X, Uzè G, Schreiber RD, Chow MT, Smyth MJ, Proietti E, André F, Kroemer G, Zitvogel L (2014) ‘Cancer cell–autonomous contribution of type i interferon signaling to the efficacy of chemotherapy’. Nat Med 20(11):1301–1309. https://doi.org/10.1038/nm.3708

  40. Zitvogel L, Apetoh L, Ghiringhelli F, Kroemer G (2008) Immunological aspects of cancer chemotherapy. Nat Rev Immunol 8(1):59–73. https://doi.org/10.1038/nri2216

  41. Keenan TE, Tolaney SM (2020) Role of immunotherapy in triple-negative breast cancer. J Natl Compr Canc Netw 18(4):479–489. https://doi.org/10.6004/jnccn.2020.7554

  42. Rugo HS, Llombart-Cussac A, Andre F, Robson ME, Saji S, Harbeck N, Schmid P, Cescon DW, Ahn JS, Nanda R, Bardia A, Fan L, Mejia JA, Karantza V (2020) ‘KEYLYNK-009: a phase II/III, Open-Label, Randomized Study of Pembrolizumab (Pembro) plus Olaparib versus Pembro plus Chemotherapy after Induction with First-Line Pembro plus Chemotherapy in Patients with Locally Recurrent Inoperable or Metastatic Triple-Negative Breast Cancer (TNBC).’ J Clin Oncol 38(15_suppl):TPS596–TPS596. https://doi.org/10.1200/JCO.2020.38.15_suppl.TPS596.

  43. Schmid P, Cortes J, Pusztai L, McArthur H, Kümmel S, Bergh J, Denkert C, Park YH, Hui R, Harbeck N, Takahashi M, Foukakis T, Fasching PA, Cardoso F, Untch M, Jia L, Karantza V, Zhao J, Aktan G, Dent R, O’Shaughnessy J (2020) Pembrolizumab for early triple-negative breast cancer. N Engl J Med 382(9):810–821. https://doi.org/10.1056/NEJMoa1910549

  44. Miles D, Gligorov J, André F, Cameron D, Schneeweiss A, Barrios C, Xu B, Wardley A, Kaen D, Andrade L, Semiglazov V, Reinisch M, Patel S, Patre M, Morales L, Patel SL, Kaul M, Barata T, O’Shaughnessy J (2021) IMpassion131 investigators. ‘Primary Results from IMpassion131, a Double-Blind, Placebo-Controlled, Randomised Phase III Trial of First-Line Paclitaxel with or without Atezolizumab for Unresectable Locally Advanced/Metastatic Triple-Negative Breast Cancer’. Annf Oncol: Official J Euro Soc Med Oncol 32(8):994–1004. https://doi.org/10.1016/j.annonc.2021.05.801

  45. Kok M, Voorwerk L, Horlings H, Sikorska K, van der Vijver K, Slagter M, Warren S, Ong S, Wiersma T, Russell N, Lalezari F, de Maaker M, Kemper I, Mandjes IA, Chalabi M, Sonke GS, Salgado R, Linn SC, Schumacher T, Blank CU (2018) ‘Adaptive Phase II Randomized Trial of Nivolumab after Induction Treatment in Triple Negative Breast Cancer (TONIC Trial): Final Response Data Stage I and First Translational Data.’ J Clin Oncol 36(15_suppl):1012–1012. https://doi.org/10.1200/JCO.2018.36.15_suppl.1012

  46. Voorwerk L, Slagter M, Horlings HM, Sikorska K, van de Vijver KK, de Maaker M, Nederlof I, Kluin RJC, Warren S, Ong S, Wiersma TG, Russell NS, Lalezari F, Schouten PC, Bakker NAM, Ketelaars SLC, Peters D, Lange CAH, van Werkhoven E, van Tinteren H, Mandjes IAM, Kemper I, Onderwater S, Chalabi M, Wilgenhof S, Haanen JBAG, Salgado R, de Visser KE, Sonke GS, Wessels LFA, Linn SC, Schumacher TN, Blank CU, Kok M (2019) ‘Immune induction strategies in metastatic triple-negative breast cancer to enhance the sensitivity to PD-1 blockade: the tonic trial’. Nat Med 25(6):920–928. https://doi.org/10.1038/s41591-019-0432-4

  47. Yardley DA, Abu-Khalaf M, Boni V, Brufsky A, Emens LA, Gutierrez M, Hurvitz S, Im SA, Loi S, McCune SL, Schmid P, O’Hear C, Zhang X, Vidal GA (2019) ‘Abstract OT2-06-04: MORPHEUS: a phase Ib/II trial platform evaluating the safety and efficacy of multiple cancer immunotherapy combinations in patients with hormone receptor–positive and triple-negative breast cancer’. Cancer Res 79(4_Supplement):OT2-06-04. https://doi.org/10.1158/1538-7445.SABCS18-OT2-06-04

  48. Nanda R, Liu MC, Yau C, Shatsky R, Pusztai L, Wallace A, Chien AJ, Forero-Torres A, Ellis E, Han H, Clark A, Albain K, Boughey JC, Jaskowiak NT, Elias A, Isaacs C, Kemmer K, Helsten T, Majure M, Stringer-Reasor E, Parker C, Lee MC, Haddad T, Cohen RN, Asare S, Wilson A, Hirst GL, Singhrao R, Steeg K, Asare A, Matthews JB, Berry S, Sanil A, Schwab R, Fraser Symmans W, van ‘t Veer L, Yee D, DeMichele A, Hylton NM, Melisko M, Perlmutter J, Rugo HS, Berry DA, Esserman LJ (2020) ‘Effect of pembrolizumab plus neoadjuvant chemotherapy on pathologic complete response in women with early-stage breast cancer’. JAMA Oncol 6(5):1–9. https://doi.org/10.1001/jamaoncol.2019.6650

  49. Gianni L, Huang CS, Egle D, Bermejo B, Zamagni C, Thill M, Anton A, Zambelli S, Bianchini G, Russo S, Ciruelos EM, Greil R, Semiglazov V, Colleoni M, Kelly C, Mariani G, Del Mastro L, Maffeis I, Valagussa P, Viale G (2022) ‘Pathologic Complete Response (PCR) to Neoadjuvant treatment with or without atezolizumab in triple-negative, early high-risk and locally advanced breast cancer: neoTRIP michelangelo randomized study’. Ann Oncol. https://doi.org/10.1016/j.annonc.2022.02.004

  50. Gianni L, Huang CS, Egle D, Bermejo B, Zamagni C, Thill M, Anton A, Zambelli S, Bianchini G, Russo S, Ciruelos EM, Greil R, Semiglazov V, Colleoni M, Kelly C, Mariani G, Del Mastro L, Maffeis I, Valagussa P, Viale G (2020) ‘Abstract GS3–04: Pathologic Complete Response (PCR) to neoadjuvant treatment with or without atezolizumab in triple negative, early high-risk and locally advanced breast cancer. NeoTRIPaPDL1 michelangelo randomized study’. Cancer Res 80(4_Supplement):GS3–04. https://doi.org/10.1158/1538-7445.SABCS19-GS3-04

  51. Loibl S, Untch M, Burchardi N, Huober J, Sinn BV, Blohmer JU, Grischke EM, Furlanetto J, Tesch H, Hanusch C, Engels K, Rezai M, Jackisch C, Schmitt WD, von Minckwitz G, Thomalla J, Kümmel S, Rautenberg B, Fasching PA, Weber K, Rhiem K, Denkert C, Schneeweiss A (2019) ‘A randomised Phase II study investigating durvalumab in addition to an anthracycline taxane-based neoadjuvant therapy in early triple-negative breast cancer: clinical results and biomarker analysis of geparnuevo study’. Ann Oncol 30(8):1279–1288. https://doi.org/10.1093/annonc/mdz158

  52. Bianchini G, Balko JM, Mayer IA, Sanders ME, Gianni L (2016) Triple-negative breast cancer: challenges and opportunities of a heterogeneous disease. Nat Rev Clin Oncol 13(11):674–690. https://doi.org/10.1038/nrclinonc.2016.66

  53. Won K-A, Spruck C (2020) ‘Triple-negative breast cancer therapy: current and future perspectives (Review)’. Int J Oncol 57(6):1245–61. https://doi.org/10.3892/ijo.2020.5135

  54. Peyraud F, Italiano A (2020) Combined PARP Inhibition and immune checkpoint therapy in solid tumors. Cancers 12(6):1502. https://doi.org/10.3390/cancers12061502

  55. Li C-W, Lim S-O, Xia W, Lee H-H, Chan L-C, Kuo C-W, Khoo K-H, Chang S-S, Cha J-H, Kim T, Hsu JL, Wu Y, Hsu J-M, Yamaguchi H, Ding Q, Wang Y, Yao J, Lee C-C, Wu H-J, Sahin AA, Allison JP, Yu D, Hortobagyi GN, Hung M-C (2016) ‘Glycosylation and stabilization of programmed death ligand-1 suppresses T-cell activity’. Nat Commun 7:12632. https://doi.org/10.1038/ncomms12632

  56. Jiao S, Xia W, Yamaguchi H, Wei Y, Chen M-K, Hsu J-M, Hsu JL, Yu W-H, Du Y, Lee H-H, Li C-W, Chou C-K, Lim S-O, Chang S-S, Litton J, Arun B, Hortobagyi GN, Hung M-C (2017) ‘PARP inhibitor upregulates PD-L1 expression and enhances cancer-associated immunosuppression’. Clin Cancer Res :Official J Am Assoc Cancer Res 23(14):3711–3720. https://doi.org/10.1158/1078-0432.CCR-16-3215

  57. Mitri ZI, Vuky J, Kemmer KA, Savin MA, Parmar S, Kolodzie Kolodzie A, Johnson B, Williams-Belizaire R, Gray JW, Mills GB (636939072000000000) ‘A Phase II trial of olaparib and durvalumab in metastatic BRCA wild type triple-negative breast cancer.’ J Clin Oncol 37(15_suppl):TPS1111–TPS1111. https://doi.org/10.1200/jco.2019.37.15_suppl.tps1111

  58. Vinayak S, Tolaney SM, Schwartzberg L, Mita M, McCann G, Tan AR, Wahner-Hendrickson AE, Forero A, Anders C, Wulf GM, Dillon P, Lynce F, Zarwan C, Erban JK, Zhou Y, Buerstatte N, Graham JR, Arora S, Dezube BJ, Telli ML (2019) ‘Open-Label clinical trial of niraparib combined with pembrolizumab for treatment of advanced or metastatic triple-negative breast cancer’. JAMA Oncol 5(8):1132–40. https://doi.org/10.1001/jamaoncol.2019.1029

  59. Domchek S, Postel-Vinay S, Im SA, Park YH, Delord JP, Italiano A, Alexandre J, You B, Bastian S, Krebs MG, Wang D, Waqar S, Lanasa M, Angell HK, Lai Z, Gresty C, Opincar LM, Herbolsheimer P, Kaufman B (2019) ‘Phase II study of Olaparib (O) and Durvalumab (D) (MEDIOLA): Updated Results in Patients (Pts) with Germline BRCA-Mutated (GBRCAm) Metastatic Breast Cancer (MBC)’. Ann Oncol 30:v477. https://doi.org/10.1093/annonc/mdz253.017

  60. Pusztai L, Yau C, Wolf DM, Han HS, Du L, Wallace AM, String-Reasor E, Boughey JC, Chien AJ, Elias AD, Beckwith H, Nanda R, Albain KS, Clark AS, Kemmer K, Kalinsky K, Isaacs C, Thomas A, Shatsky R, Helsten TL, Forero-Torres A, Liu MC, Brown-Swigart L, Petricoin EF, Wulfkuhle JD, Asare SM, Wilson A, Singhrao R, Sit L, Hirst GL, Berry S, Sanil A, Asare AL, Matthews JB, Perlmutter J, Melisko M, Rugo HS, Schwab RB, Fraser Symmans W, Yee D, Van’t Veer LJ, Hylton NM, DeMichele AM, Berry DA, Esserman LJ ( 2021) ‘Durvalumab with olaparib and paclitaxel for high-risk HER2-negative stage II/III breast cancer: results from the adaptively randomized I-SPY2 trial’. Cancer Cell 39(7):989-998.e5. https://doi.org/10.1016/j.ccell.2021.05.009

  61. Friedlander M, Meniawy T, Markman B, Mileshkin L, Harnett P, Millward M, Lundy J, Freimund A, Norris C, Mu S, Wu J, Paton V, Gao B (2019) ‘Pamiparib in combination with tislelizumab in patients with advanced solid tumours: results from the dose-escalation stage of a multicentre, open-label, phase 1a/b trial’. Lancet Oncol 20(9):1306–15. https://doi.org/10.1016/S1470-2045(19)30396-1

  62. Kandalaft LE, Motz GT, Busch J, Coukos G (2011) ‘Angiogenesis and the Tumor vasculature as antitumor immune modulators: the role of vascular endothelial growth factor and endothelin’. In: Dranoff G (ed) Cancer immunology and immunotherapy. Springer, Berlin, pp 129–148

    Google Scholar 

  63. Zimmer AS, Nichols E, Cimino-Mathews A, Peer C, Cao L, Lee M-J, Kohn EC, Annunziata CM, Lipkowitz S, Trepel JB, Sharma R, Mikkilineni L, Gatti-Mays M, Figg WD, Houston ND, Lee J-M (2019) ‘A phase I study of the PD-L1 inhibitor, durvalumab, in combination with a PARP inhibitor, olaparib, and a VEGFR1–3 inhibitor, cediranib, in recurrent women’s cancers with biomarker analyses’. J ImmunoTherapy Cancer 7(1):197. https://doi.org/10.1186/s40425-019-0680-3

  64. George S, Miao D, Demetri GD, Adeegbe D, Rodig SJ, Shukla S, Lipschitz M, Amin-Mansour A, Raut CP, Carter SL, Hammerman P, Freeman GJ, Wu CJ, Ott PA, Wong K-K, Van Allen EM (2017) ‘Loss of PTEN associated with resistance to anti-PD-1 checkpoint blockade therapy in metastatic uterine leiomyosarcoma’. Immunity 46(2):197–204. https://doi.org/10.1016/j.immuni.2017.02.001

  65. Peng W, Chen JQ, Liu C, Malu S, Creasy C, Tetzlaff MT, Xu C, McKenzie JA, Zhang C, Liang X, Williams LJ, Deng W, Chen G, Mbofung R, Lazar AJ, Torres-Cabala CA, Cooper ZA, Chen P-L, Tieu TN, Spranger S, Yu X, Bernatchez C, Forget M-A, Haymaker C, Amaria R, McQuade JL, Glitza IC, Cascone T, Li HS, Kwong LN, Heffernan TP, Hu J, Bassett RL, Bosenberg MW, Woodman SE, Overwijk WW, Lizée G, Roszik J, Gajewski TF, Wargo JA, Gershenwald JE, Radvanyi L, Davies MA, Hwu P (2016) ‘Loss of PTEN promotes resistance to T cell-mediated immunotherapy’. Cancer Discov 6(2):202–216. https://doi.org/10.1158/2159-8290.CD-15-0283

  66. Schmid P, Savas P, Espinosa E, Boni V, Italiano A, White S, Cheng K, Lam L, Robert L, Laliman V, Shah K, Sablin M-P (2021) ‘Abstract PS12–28: phase 1b study evaluating a triplet combination of Ipatasertib (IPAT), atezolizumab, and a taxane as first-line therapy for locally advanced/metastatic Triple-Negative Breast Cancer (TNBC)’. Cancer Res 81(4_Supplement):PS12–28. https://doi.org/10.1158/1538-7445.SABCS20-PS12-28

  67. Tolaney SM, Kalinsky K, Kaklamani VG, D’Adamo DR, Aktan G, Tsai ML, O’Regan R, Kaufman PA, Wilks S, Andreopoulou E, Patt DA, Yuan Y, Wang G, Xing D, Kleynerman E, Karantza V, Diab S (2020) A phase Ib/II study of eribulin (ERI) plus pembrolizumab (PEMBRO) in metastatic triple-negative breast cancer (MTNBC) (ENHANCE 1). J Clin Oncol 38(15_suppl):1015–1015. https://doi.org/10.1200/JCO.2020.38.15_suppl.1015

  68. Fares CM, Van Allen EM, Drake CG, Allison JP, Hu-Lieskovan S (2019) ‘Mechanisms of resistance to immune checkpoint blockade: why does checkpoint inhibitor immunotherapy not work for all patients?’ Am Soc Clin Oncol Educ Book (39):147–64. https://doi.org/10.1200/EDBK_240837

  69. Baumann D, Hägele T, Mochayedi J, Drebant J, Vent C, Blobner S, Noll JH, Nickel I, Schumacher C, Boos SL, Daniel AS, Wendler S, Volkmar M, Strobel O, Offringa R (2020) Proimmunogenic impact of MEK inhibition synergizes with agonist anti-CD40 immunostimulatory antibodies in tumor therapy. Nat Commun 11:2176. https://doi.org/10.1038/s41467-020-15979-2

  70. Ribas A, Algazi A, Ascierto PA, Butler MO, Chandra S, Gordon M, Hernandez-Aya L, Lawrence D, Lutzky J, Miller WH, Campbell KM, Delafont B, Marshall S, Mueller N, Robert C (2020) PD-L1 Blockade in combination with inhibition of MAPK oncogenic signaling in patients with advanced melanoma. Nat Commun 11:6262. https://doi.org/10.1038/s41467-020-19810-w

  71. Loi S, Dushyanthen S, Beavis PA, Salgado R, Denkert C, Savas P, Combs S, Rimm DL, Giltnane JM, Estrada MV, Sánchez V, Sanders ME, Cook RS, Pilkinton MA, Mallal SA, Wang K, Miller VA, Stephens PJ, Yelensky R, Doimi FD, Gómez H, Ryzhov SV, Darcy PK, Arteaga CL, Balko JM (2016) RAS/MAPK Activation is associated with reduced tumor-infiltrating lymphocytes in triple-negative breast cancer: therapeutic cooperation between MEK and PD-1/PD-L1 Immune checkpoint inhibitors. Clin Cancer Res Official J Am Assoc Cancer Res 22(6):1499–1509. https://doi.org/10.1158/1078-0432.CCR-15-1125

  72. Brufsky A, Kim S-B, Zvirbule Z, Dirix LY, Eniu AE, Carabantes F, Izarzugaza Y, Mebis J, Sohn J, Wongchenko M, Chohan S, Amin R, McNally VA, Miles D, Loi S (2019) ‘Phase II COLET Study: Atezolizumab (A) + Cobimetinib (C) + Paclitaxel (P)/Nab-Paclitaxel (NP) as First-Line (1L) Treatment (Tx) for Patients (Pts) with Locally Advanced or Metastatic Triple-Negative Breast Cancer (MTNBC).’ J Clin Oncol 37(15_suppl):1013–1013. https://doi.org/10.1200/JCO.2019.37.15_suppl.1013

  73. Yang B, Li X, Fu Y, Guo E, Ye Y, Li F, Liu S, Xiao R, Liu C, Lu F, Huang J, Qin T, Han L, Peng G, Mills GB, Sun C, Chen G (2021) ‘MEK inhibition remodels the immune landscape of mutant KRAS tumors to overcome resistance to PARP and immune checkpoint inhibitors’. Cancer Res 81(10):2714–29. https://doi.org/10.1158/0008-5472.CAN-20-2370

  74. Wells AD, Morawski PA (2014) New roles for cyclin-dependent kinases in t cell biology: linking cell division and differentiation. Nat Rev Immunol 14(4):261–270. https://doi.org/10.1038/nri3625

  75. Goel S, DeCristo MJ, Watt AC, BrinJones H, Sceneay J, Li BB, Khan N, Ubellacker JM, Xie S, Metzger-Filho O, Hoog J, Ellis MJ, Ma C, Ramm S, Krop IE, Winer EP, Roberts TM, Kim H-J, McAllister SS, Zhao JJ (2017) CDK4/6 Inhibition triggers anti-tumor immunity. Nature 548(7668):471–475. https://doi.org/10.1038/nature23465

  76. Deng J, Wang ES, Jenkins RW, Li S, Dries R, Yates K, Chhabra S, Huang W, Liu H, Aref AR, Ivanova E, Paweletz CP, Bowden M, Zhou CW, Herter-Sprie GS, Sorrentino JA, Bisi JE, Lizotte PH, Merlino AA, Quinn MM, Bufe LE, Yang A, Zhang Y, Zhang H, Gao P, Chen T, Cavanaugh ME, Rode AJ, Haines E, Roberts PJ, Strum JC, Richards WG, Lorch JH, Parangi S, Gunda V, Boland GM, Bueno R, Palakurthi S, Freeman GJ, Ritz J, Haining WN, Sharpless NE, Arthanari H, Shapiro GI, Barbie DA, Gray NS, Wong K-K (2018) ‘CDK4/6 inhibition augments anti-tumor immunity by enhancing T cell activation’. Cancer Discov 8(2):216–33. https://doi.org/10.1158/2159-8290.CD-17-0915

  77. Sasada T, Noguchi M, Yamada A, Itoh K (2012) Personalized peptide vaccination: a novel immunotherapeutic approach for advanced cancer. Hum Vaccin Immunother 8(9):1309–1313. https://doi.org/10.4161/hv.20988

  78. Kleponis J, Skelton R, Zheng L (2015) Fueling the engine and releasing the break: combinational therapy of cancer vaccines and immune checkpoint inhibitors. Cancer Biol Med 12(3):201–208. https://doi.org/10.7497/j.issn.2095-3941.2015.0046

  79. Corti C, Giachetti PPMB, Eggermont AMM, Delaloge S, Curigliano G (2022) Therapeutic vaccines for breast cancer: has the time finally come? Eur J Cancer 160:150–174. https://doi.org/10.1016/j.ejca.2021.10.027

  80. Salagianni M, Baxevanis CN, Papamichail M, Perez SA (2012) New insights into the role of nk cells in cancer immunotherapy. Oncoimmunology 1(2):205–207. https://doi.org/10.4161/onci.1.2.18398

  81. Zhu H, Blum RH, Bjordahl R, Gaidarova S, Rogers P, Lee TT, Abujarour R, Bonello GB, Wu J, Tsai P-F, Miller JS, Walcheck B, Valamehr B, Kaufman DS (2020) ‘Pluripotent stem cell-derived NK cells with high-affinity noncleavable CD16a mediate improved antitumor activity’. Blood 135(6):399–410. https://doi.org/10.1182/blood.2019000621

  82. Fabian KP, Hodge JW (2021) The emerging role of off-the-shelf engineered natural killer cells in targeted cancer immunotherapy. Mol Ther-Oncolytics 23:266–276. https://doi.org/10.1016/j.omto.2021.10.001

  83. Blank CU, Haanen JB, Ribas A, Schumacher TN (2016) ‘Cancer immunology. The “Cancer Immunogram”’. Science (New York, N.Y.) 352(6286):658–660. https://doi.org/10.1126/science.aaf2834

  84. Kwa MJ, Adams S (2018) Checkpoint Inhibitors in Triple-Negative Breast Cancer (TNBC): Where to go from here. Cancer 124(10):2086–2103. https://doi.org/10.1002/cncr.31272

  85. Arora S, Velichinskii R, Lesh RW, Ali U, Kubiak M, Bansal P, Borghaei H, Edelman MJ, Boumber Y (2019) Existing and emerging biomarkers for immune checkpoint immunotherapy in solid tumors. Adv Ther 36(10):2638–2678. https://doi.org/10.1007/s12325-019-01051-z

  86. Erber R, Hartmann A (2020) Understanding PD-L1 Testing in breast cancer: a practical approach. Breast Care 15(5):481–490. https://doi.org/10.1159/000510812

  87. Ribas A, Hu-Lieskovan S (2016) ‘What Does PD-L1 positive or negative mean?’ J Exp Med 213(13):2835–2840. https://doi.org/10.1084/jem.20161462

  88. Kwon M, Jung H, Nam G-H, Kim I-S (2021) The right timing, right combination, right sequence, and right delivery for cancer immunotherapy. J Control Release 331:321–334. https://doi.org/10.1016/j.jconrel.2021.01.009

  89. Tan Q, Yin S, Zhou D, Chi Y, Man X, Li H (2022) Potential predictive and prognostic value of biomarkers related to immune checkpoint inhibitor therapy of triple-negative breast cancer. Front Oncol 12:779786. https://doi.org/10.3389/fonc.2022.779786

  90. El Bairi K, Haynes HR, Blackley E, Fineberg S, Shear J, Turner S, Ribeiro de Freitas J, Sur D, Amendola LC, Gharib M, Kallala A, Arun I, Azmoudeh-Ardalan F, Fujimoto L, Sua LF, Liu S-W, Lien H-C, Kirtani P, Balancin M, El Attar H, Guleria P, Yang W, Shash E, Chen I-C, Bautista V, Fernando Do Prado Moura J, Rapoport BL, Castaneda C, Spengler E, Acosta-Haab G, Frahm I, Sanchez J, Castillo M, Bouchmaa N, Zin RRM, Shui R, Onyuma T, Yang W, Husain Z, Willard-Gallo K, Coosemans A, Perez EA, Provenzano E, Gonzalez Ericsson P, Richardet E, Mehrotra R, Sarancone S, Ehinger A, Rimm DL, Bartlett JMS, Viale G, Denkert C, Hida AI, Sotiriou C, Loibl S, Hewitt SM, Badve S, Symmans WF, Kim RS, Pruneri G, Goel S, Francis PA, Inurrigarro G, Yamaguchi R, Garcia-Rivello H, Horlings H, Afqir S, Salgado R, Adams S, Kok M, Vittoria Dieci M, Michiels S, Demaria S, Loi S (2021) ‘The tale of TILs in breast cancer: a report from the international immuno-oncology biomarker working group’. Npj Breast Cancer 7(1):1–17. https://doi.org/10.1038/s41523-021-00346-1

  91. Carlino F, Diana A, Piccolo A, Ventriglia A, Bruno V, De Santo I, Letizia O, De Vita F, Daniele B, Ciardiello F, Orditura M (2022) Immune-based therapy in triple-negative breast cancer: from molecular biology to clinical practice. Cancers 14(9):2102. https://doi.org/10.3390/cancers14092102

  92. Tolaney SM, Kabos P, Dickler MN, Gianni L, Jansen V, Lu Y, Young S, and Hope S. Rugo. 2018. ‘Updated Efficacy, Safety, & PD-L1 Status of Patients with HR+, HER2- Metastatic Breast Cancer Administered Abemaciclib plus Pembrolizumab.’ J Clin Oncol 36(15_suppl):1059–1059. https://doi.org/10.1200/JCO.2018.36.15_suppl.1059

  93. Savas P, Virassamy B, Ye C, Salim A, Mintoff CP, Caramia F, Salgado R, Byrne DJ, Teo ZL, Dushyanthen S, Byrne A, Wein L, Luen SJ, Poliness C, Nightingale SS, Skandarajah AS, Gyorki DE, Thornton CM, Beavis PA, Fox SB, Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer (kConFab); Darcy PK, Speed TP, Mackay LK, Neeson PJ, Loi S (2018) ‘Single-cell profiling of breast cancer T cells reveals a tissue-resident memory subset associated with improved prognosis’. Nat Med 24(7):986–993. https://doi.org/10.1038/s41591-018-0078-7

  94. Bertucci F, Finetti P, Simeone I, Hendrickx W, Wang E, Marincola FM, Viens P, Mamessier E, Ceccarelli M, Birnbaum D, Bedognetti D (2018) The immunologic constant of rejection classification refines the prognostic value of conventional prognostic signatures in breast cancer. Br J Cancer 119(11):1383–1391. https://doi.org/10.1038/s41416-018-0309-1

  95. Hendrickx W, Simeone I, Anjum S, Mokrab Y, Bertucci F, Finetti P, Curigliano G, Seliger B, Cerulo L, Tomei S, Delogu LG, Maccalli C, Wang E, Miller LD, Marincola FM, Ceccarelli M, Bedognetti D (2017) Identification of genetic determinants of breast cancer immune phenotypes by integrative genome-scale analysis. Oncoimmunology 6(2):e1253654. https://doi.org/10.1080/2162402X.2016.1253654

  96. Samstein RM, Lee C-H, Shoushtari AN, Hellmann MD, Shen R, Janjigian YY, Barron DA, Zehir A, Jordan EJ, Omuro A, Kaley TJ, Kendall SM, Motzer RJ, Hakimi AA, Voss MH, Russo P, Rosenberg J, Iyer G, Bochner BH, Bajorin DF, Al-Ahmadie HA, Chaft JE, Rudin CM, Riely GJ, Baxi S, Ho AL, Wong RJ, Pfister DG, Wolchok JD, Barker CA, Gutin PH, Brennan C, Tabar V, Mellinghoff IK, DeAngelis LM, Ariyan CE, Lee N, Tap WD, Gounder MM, D’Angelo SP, Saltz L, Stadler ZK, Scher HI, Baselga J, Razavi P, Klebanoff CA, Yaeger R, Segal NH, Ku GY, DeMatteo RP, Ladanyi M, Rizvi NA, Berger MF, Riaz N, Solit DB, Chan TA, Morris LGT (2019) ‘Tumor mutational load predicts survival after immunotherapy across multiple cancer types’. Nat Genet 51(2):202–226. https://doi.org/10.1038/s41588-018-0312-8

  97. Bonneville R, Krook MA, Kautto EA, Miya J, Wing MR, Chen H-Z, Reeser JW, Yu L, Roychowdhury S (2017) ‘Landscape of microsatellite instability across 39 cancer types’. JCO Precision Oncol 1:PO.17.00073. https://doi.org/10.1200/PO.17.00073

  98. Wu S, Shi X, Wang J, Wang X, Liu Y, Luo Y, Mao F, Zeng X (2021) Triple-negative breast cancer: intact mismatch repair and partial co-expression of PD-L1 and LAG-3. Front Immunol 12:561793. https://doi.org/10.3389/fimmu.2021.561793

  99. Marcus L, Lemery SJ, Keegan P, Pazdur R (2019) FDA Approval summary: pembrolizumab for the treatment of microsatellite instability-high solid tumors. Clin Cancer Res: Official J Am Assoc Cancer Res 25(13):3753–3758. https://doi.org/10.1158/1078-0432.CCR-18-4070

  100. Venetis K, Sajjadi E, Haricharan S, Fusco N (2020) ‘Mismatch repair testing in breast cancer: the path to tumor-specific immuno-oncology biomarkers’. Transl Cancer Res 9(7). https://doi.org/10.21037/tcr-20-1852

  101. Marra A, Viale G, Curigliano G (2019) Recent advances in triple negative breast cancer: the immunotherapy era. BMC Med 17:90. https://doi.org/10.1186/s12916-019-1326-5

  102. Robson M, Im S-A, Senkus E, Xu B, Domchek SM, Masuda N, Delaloge S, Li W, Tung N, Armstrong A, Wu W, Goessl C, Runswick S, Conte P (2017) ‘Olaparib for metastatic breast cancer in patients with a germline BRCA mutation’. New England J Med 377(6):523–33. https://doi.org/10.1056/NEJMoa1706450

  103. Nolan E, Savas P, Policheni AN, Darcy PK, Vaillant F, Mintoff CP, Dushyanthen S, Mansour M, Pang J-MB, Fox SB, Perou CM, Visvader JE, Gray DHD, Loi S, Lindeman GJ (2017) ‘Combined Immune checkpoint blockade as a therapeutic strategy for BRCA1-mutated breast cancer’. Sci Trans Med 9(393):eaal4922. https://doi.org/10.1126/scitranslmed.aal4922

  104. Sun W, Zhang Q, Wang R, Li Y, Sun Y, Yang L (2021) Targeting DNA damage repair for immune checkpoint inhibition: mechanisms and potential clinical applications. Front Oncol 11:648687. https://doi.org/10.3389/fonc.2021.648687

  105. Mouw KW, Goldberg MS, Konstantinopoulos PA, D’Andrea AD (2017) DNA Damage and repair biomarkers of immunotherapy response. Cancer Discov 7(7):675–693. https://doi.org/10.1158/2159-8290.CD-17-0226

  106. Vinayak S, Tolaney SM, Schwartzberg LS, Mita MM, Anne-Lee McCann G, Tan AR, Hendrickson AEW, Forero-Torres A, Anders CK, Wulf GM, Dillon PM, Lynce F, Zarwan C, Erban JK, Dezube BJ, Zhou Y, Buerstatte N, Arora S, Achour H, Telli ML (2018) ‘TOPACIO/Keynote-162: Niraparib + Pembrolizumab in Patients (Pts) with Metastatic Triple-Negative Breast Cancer (TNBC), a Phase 2 Trial.’ J Clin Oncol 36(15_suppl):1011–1011. https://doi.org/10.1200/JCO.2018.36.15_suppl.101

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  1. Faculty of Medicine and Pharmacy, Mohammed Ist University, Oujda, Morocco

    Ouissam Al Jarroudi, Khalid El Bairi & Said Afqir

  2. Department of Medical Oncology, Mohammed VI University Hospital, Oujda, Morocco

    Ouissam Al Jarroudi, Khalid El Bairi & Said Afqir

  3. European Institute of Oncology, IRCCS, Milan, Italy

    Giuseppe Curigliano

  4. Department of Oncology and Hematology, University of Milan, Milan, Italy

    Giuseppe Curigliano

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    Ouissam Al Jarroudi

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    Khalid El Bairi

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Jarroudi, O.A., Bairi, K.E., Curigliano, G., Afqir, S. (2023). Immune-Checkpoint Inhibitors: A New Line of Attack in Triple-Negative Breast Cancer. In: Al Jarroudi, O., El Bairi, K., Curigliano, G. (eds) Breast Cancer Research and Treatment. Cancer Treatment and Research, vol 188. Springer, Cham. https://doi.org/10.1007/978-3-031-33602-7_2

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