Skip to main content

Advertisement

SpringerLink
Log in

Prognostic implication of CTLA-4, PD-1, and PD-L1 expression in aggressive adult T-cell leukemia–lymphoma

  • Original Article
  • Published:
Annals of Hematology Aims and scope Submit manuscript

Abstract

The prognosis of patients with aggressive adult T cell leukemia–lymphoma (ATLL) is dismal even with intensive chemotherapy. Allogeneic hematopoietic stem cell transplantation (HSCT) is a promising option for patients with aggressive ATLL, but the posttransplant outcome remains unsatisfactory. Hence, to further improve clinical outcomes, novel therapeutic approaches are needed. The clinical significance of immune checkpoint protein expression has not been well-established in aggressive ATLL. This study aims to identify the association between the expression profile of immune checkpoint proteins on ATLL cells and clinical outcomes. This retrospective study cohort included 65 patients with aggressive ATLL diagnosed between 2001 and 2015 at the National Cancer Center Hospital, Tokyo, Japan. Formalin-fixed paraffin-embedded tissue was used to immunohistochemically determine the expression of immune checkpoint proteins and assess the impact of expression profile on the probability of overall survival from diagnosis or HSCT. The current analysis shows that cytotoxic T lymphocyte antigen-4 (CTLA-4), programmed death-1 (PD-1), and programmed death-ligand 1 (PD-L1) expressions were adverse prognostic factors in patients with aggressive ATLL. Experiments that assess the efficacy of immune checkpoint inhibitors are warranted to alleviate the adverse impacts associated with negative immune checkpoints.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Ishitsuka K, Tamura K (2014) Human T-cell leukaemia virus type I and adult T-cell leukaemia-lymphoma. Lancet Oncol 15(11):e517-526. https://doi.org/10.1016/s1470-2045(14)70202-5

    Article  CAS  PubMed  Google Scholar 

  2. Shimoyama M (1991) Diagnostic criteria and classification of clinical subtypes of adult T-cell leukaemia-lymphoma. A report from the Lymphoma Study Group (1984–87). Br J Haematol 79(3):428–437. https://doi.org/10.1111/j.1365-2141.1991.tb08051.x

    Article  CAS  PubMed  Google Scholar 

  3. Imaizumi Y, Iwanaga M, Nosaka K, Ishitsuka K, Ishizawa K, Ito S, Amano M, Ishida T, Uike N, Utsunomiya A, Ohshima K, Tanaka J, Tokura Y, Tobinai K, Watanabe T, Uchimaru K, Tsukasaki K (2020) Prognosis of patients with adult T-cell leukemia/lymphoma in Japan: a nationwide hospital-based study. Cancer Sci 111(12):4567–4580. https://doi.org/10.1111/cas.14658

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Tsukasaki K, Hermine O, Bazarbachi A, Ratner L, Ramos JC, Harrington W Jr, O’Mahony D, Janik JE, Bittencourt AL, Taylor GP, Yamaguchi K, Utsunomiya A, Tobinai K, Watanabe T (2009) Definition, prognostic factors, treatment, and response criteria of adult T-cell leukemia-lymphoma: a proposal from an international consensus meeting. J Clin Oncol 27(3):453–459. https://doi.org/10.1200/jco.2008.18.2428

    Article  PubMed  PubMed Central  Google Scholar 

  5. Katsuya H, Yamanaka T, Ishitsuka K, Utsunomiya A, Sasaki H, Hanada S, Eto T, Moriuchi Y, Saburi Y, Miyahara M, Sueoka E, Uike N, Yoshida S, Yamashita K, Tsukasaki K, Suzushima H, Ohno Y, Matsuoka H, Jo T, Suzumiya J, Tamura K (2012) Prognostic index for acute- and lymphoma-type adult T-cell leukemia/lymphoma. J Clin Oncol 30(14):1635–1640. https://doi.org/10.1200/jco.2011.38.2101

    Article  CAS  PubMed  Google Scholar 

  6. Tsukasaki K, Utsunomiya A, Fukuda H, Shibata T, Fukushima T, Takatsuka Y, Ikeda S, Masuda M, Nagoshi H, Ueda R, Tamura K, Sano M, Momita S, Yamaguchi K, Kawano F, Hanada S, Tobinai K, Shimoyama M, Hotta T, Tomonaga M (2007) VCAP-AMP-VECP compared with biweekly CHOP for adult T-cell leukemia-lymphoma: Japan Clinical Oncology Group Study JCOG9801. J Clin Oncol 25(34):5458–5464. https://doi.org/10.1200/jco.2007.11.9958

    Article  CAS  PubMed  Google Scholar 

  7. Fukushima T, Nomura S, Shimoyama M, Shibata T, Imaizumi Y, Moriuchi Y, Tomoyose T, Uozumi K, Kobayashi Y, Fukushima N, Utsunomiya A, Tara M, Nosaka K, Hidaka M, Uike N, Yoshida S, Tamura K, Ishitsuka K, Kurosawa M, Nakata M, Fukuda H, Hotta T, Tobinai K, Tsukasaki K (2014) Japan Clinical Oncology Group (JCOG) prognostic index and characterization of long-term survivors of aggressive adult T-cell leukaemia-lymphoma (JCOG0902A). Br J Haematol 166(5):739–748. https://doi.org/10.1111/bjh.12962

    Article  PubMed  Google Scholar 

  8. Cook LB, Fuji S, Hermine O, Bazarbachi A, Ramos JC, Ratner L, Horwitz S, Fields P, Tanase A, Bumbea H, Cwynarski K, Taylor G, Waldmann TA, Bittencourt A, Marcais A, Suarez F, Sibon D, Phillips A, Lunning M, Farid R, Imaizumi Y, Choi I, Ishida T, Ishitsuka K, Fukushima T, Uchimaru K, Takaori-Kondo A, Tokura Y, Utsunomiya A, Matsuoka M, Tsukasaki K, Watanabe T (2019) Revised Adult T-Cell Leukemia-Lymphoma International Consensus Meeting Report. J Clin Oncol 37(8):677–687. https://doi.org/10.1200/JCO.18.00501

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Malpica L, Pimentel A, Reis IM, Gotuzzo E, Lekakis L, Komanduri K, Harrington T, Barber GN, Ramos JC (2018) Epidemiology, clinical features, and outcome of HTLV-1-related ATLL in an area of prevalence in the United States. Blood Adv 2(6):607–620. https://doi.org/10.1182/bloodadvances.2017011106

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Hishizawa M, Kanda J, Utsunomiya A, Taniguchi S, Eto T, Moriuchi Y, Tanosaki R, Kawano F, Miyazaki Y, Masuda M, Nagafuji K, Hara M, Takanashi M, Kai S, Atsuta Y, Suzuki R, Kawase T, Matsuo K, Nagamura-Inoue T, Kato S, Sakamaki H, Morishima Y, Okamura J, Ichinohe T, Uchiyama T (2010) Transplantation of allogeneic hematopoietic stem cells for adult T-cell leukemia: a nationwide retrospective study. Blood 116(8):1369–1376. https://doi.org/10.1182/blood-2009-10-247510

    Article  CAS  PubMed  Google Scholar 

  11. Ishida T, Hishizawa M, Kato K, Tanosaki R, Fukuda T, Taniguchi S, Eto T, Takatsuka Y, Miyazaki Y, Moriuchi Y, Hidaka M, Akashi K, Uike N, Sakamaki H, Morishima Y, Kato K, Suzuki R, Nishiyama T, Utsunomiya A (2012) Allogeneic hematopoietic stem cell transplantation for adult T-cell leukemia-lymphoma with special emphasis on preconditioning regimen: a nationwide retrospective study. Blood 120(8):1734–1741. https://doi.org/10.1182/blood-2012-03-414490

    Article  CAS  PubMed  Google Scholar 

  12. Kanda J, Hishizawa M, Utsunomiya A, Taniguchi S, Eto T, Moriuchi Y, Tanosaki R, Kawano F, Miyazaki Y, Masuda M, Nagafuji K, Hara M, Takanashi M, Kai S, Atsuta Y, Suzuki R, Kawase T, Matsuo K, Nagamura-Inoue T, Kato S, Sakamaki H, Morishima Y, Okamura J, Ichinohe T, Uchiyama T (2012) Impact of graft-versus-host disease on outcomes after allogeneic hematopoietic cell transplantation for adult T-cell leukemia: a retrospective cohort study. Blood 119(9):2141–2148. https://doi.org/10.1182/blood-2011-07-368233

    Article  CAS  PubMed  Google Scholar 

  13. Fujiwara H, Fuji S, Wake A, Kato K, Takatsuka Y, Fukuda T, Taguchi J, Uchida N, Miyamoto T, Hidaka M, Miyazaki Y, Tomoyose T, Onizuka M, Takanashi M, Ichinohe T, Atsuta Y, Utsunomiya A, Transplantation ATLWGotJSfHC, (2017) Dismal outcome of allogeneic hematopoietic stem cell transplantation for relapsed adult T-cell leukemia/lymphoma, a Japanese nation-wide study. Bone Marrow Transplant 52(3):484–488. https://doi.org/10.1038/bmt.2016.313

    Article  CAS  PubMed  Google Scholar 

  14. Fuji S, Inoue Y, Utsunomiya A, Moriuchi Y, Uchimaru K, Choi I, Otsuka E, Henzan H, Kato K, Tomoyose T, Yamamoto H, Kurosawa S, Matsuoka K, Yamaguchi T, Fukuda T (2016) Pretransplantation anti-CCR4 antibody mogamulizumab against adult t-cell leukemia/lymphoma is associated with significantly increased risks of severe and corticosteroid-refractory graft-versus-host disease, nonrelapse mortality, and overall mortality. J Clin Oncol 34(28):3426–3433. https://doi.org/10.1200/jco.2016.67.8250

    Article  PubMed  Google Scholar 

  15. Muenst S, Hoeller S, Willi N, Dirnhofera S, Tzankov A (2010) Diagnostic and prognostic utility of PD-1 in B cell lymphomas. Dis Markers 29(1):47–53. https://doi.org/10.3233/dma-2010-0725

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Cetinozman F, Jansen PM, Vermeer MH, Willemze R (2012) Differential expression of programmed death-1 (PD-1) in Sezary syndrome and mycosis fungoides. Arch Dermatol 148(12):1379–1385. https://doi.org/10.1001/archdermatol.2012.2089

    Article  PubMed  Google Scholar 

  17. Cetinozman F, Jansen PM, Willemze R (2012) Expression of programmed death-1 in primary cutaneous CD4-positive small/medium-sized pleomorphic T-cell lymphoma, cutaneous pseudo-T-cell lymphoma, and other types of cutaneous T-cell lymphoma. Am J Surg Pathol 36(1):109–116. https://doi.org/10.1097/PAS.0b013e318230df87

    Article  PubMed  Google Scholar 

  18. Richendollar BG, Pohlman B, Elson P, Hsi ED (2011) Follicular programmed death 1-positive lymphocytes in the tumor microenvironment are an independent prognostic factor in follicular lymphoma. Hum Pathol 42(4):552–557. https://doi.org/10.1016/j.humpath.2010.08.015

    Article  CAS  PubMed  Google Scholar 

  19. Gravelle P, Burroni B, Pericart S, Rossi C, Bezombes C, Tosolini M, Damotte D, Brousset P, Fournie JJ, Laurent C (2017) Mechanisms of PD-1/PD-L1 expression and prognostic relevance in non-Hodgkin lymphoma: a summary of immunohistochemical studies. Oncotarget 8(27):44960–44975. https://doi.org/10.18632/oncotarget.16680

    Article  PubMed  PubMed Central  Google Scholar 

  20. Smeltzer JP, Jones JM, Ziesmer SC, Grote DM, Xiu B, Ristow KM, Yang ZZ, Nowakowski GS, Feldman AL, Cerhan JR, Novak AJ, Ansell SM (2014) Pattern of CD14+ follicular dendritic cells and PD1+ T cells independently predicts time to transformation in follicular lymphoma. Clin Cancer Res 20(11):2862–2872. https://doi.org/10.1158/1078-0432.ccr-13-2367

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Yang ZZ, Grote DM, Ziesmer SC, Xiu B, Novak AJ, Ansell SM (2015) PD-1 expression defines two distinct T-cell sub-populations in follicular lymphoma that differentially impact patient survival. Blood Cancer J 5:e281. https://doi.org/10.1038/bcj.2015.1

    Article  PubMed  PubMed Central  Google Scholar 

  22. Zhang W, Bai JF, Zuo MX, Cao XX, Chen M, Zhang Y, Han X, Zhong DR, Zhou DB (2016) PD-1 expression on the surface of peripheral blood CD4+ T cell and its association with the prognosis of patients with diffuse large B-cell lymphoma. Cancer Med 5(11):3077–3084. https://doi.org/10.1002/cam4.874

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Dorfman DM, Brown JA, Shahsafaei A, Freeman GJ (2006) Programmed death-1 (PD-1) is a marker of germinal center-associated T cells and angioimmunoblastic T-cell lymphoma. Am J Surg Pathol 30(7):802–810. https://doi.org/10.1097/01.pas.0000209855.28282.ce

    Article  PubMed  PubMed Central  Google Scholar 

  24. Xerri L, Chetaille B, Serriari N, Attias C, Guillaume Y, Arnoulet C, Olive D (2008) Programmed death 1 is a marker of angioimmunoblastic T-cell lymphoma and B-cell small lymphocytic lymphoma/chronic lymphocytic leukemia. Hum Pathol 39(7):1050–1058. https://doi.org/10.1016/j.humpath.2007.11.012

    Article  CAS  PubMed  Google Scholar 

  25. Laurent C, Charmpi K, Gravelle P, Tosolini M, Franchet C, Ysebaert L, Brousset P, Bidaut A, Ycart B, Fournie JJ (2015) Several immune escape patterns in non-Hodgkin’s lymphomas. Oncoimmunology 4(8):e1026530. https://doi.org/10.1080/2162402x.2015.1026530

    Article  PubMed  PubMed Central  Google Scholar 

  26. Wahlin BE, Aggarwal M, Montes-Moreno S, Gonzalez LF, Roncador G, Sanchez-Verde L, Christensson B, Sander B, Kimby E (2010) A unifying microenvironment model in follicular lymphoma: outcome is predicted by programmed death-1–positive, regulatory, cytotoxic, and helper T cells and macrophages. Clin Cancer Res 16(2):637–650. https://doi.org/10.1158/1078-0432.ccr-09-2487

    Article  CAS  PubMed  Google Scholar 

  27. Wilcox RA, Feldman AL, Wada DA, Yang ZZ, Comfere NI, Dong H, Kwon ED, Novak AJ, Markovic SN, Pittelkow MR, Witzig TE, Ansell SM (2009) B7–H1 (PD-L1, CD274) suppresses host immunity in T-cell lymphoproliferative disorders. Blood 114(10):2149–2158. https://doi.org/10.1182/blood-2009-04-216671

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Kwon D, Kim S, Kim PJ, Go H, Nam SJ, Paik JH, Kim YA, Kim TM, Heo DS, Kim CW, Jeon YK (2016) Clinicopathological analysis of programmed cell death 1 and programmed cell death ligand 1 expression in the tumour microenvironments of diffuse large B cell lymphomas. Histopathology 68(7):1079–1089. https://doi.org/10.1111/his.12882

    Article  PubMed  Google Scholar 

  29. Menter T, Bodmer-Haecki A, Dirnhofer S, Tzankov A (2016) Evaluation of the diagnostic and prognostic value of PDL1 expression in Hodgkin and B-cell lymphomas. Hum Pathol 54:17–24. https://doi.org/10.1016/j.humpath.2016.03.005

    Article  CAS  PubMed  Google Scholar 

  30. Kiyasu J, Miyoshi H, Hirata A, Arakawa F, Ichikawa A, Niino D, Sugita Y, Yufu Y, Choi I, Abe Y, Uike N, Nagafuji K, Okamura T, Akashi K, Takayanagi R, Shiratsuchi M, Ohshima K (2015) Expression of programmed cell death ligand 1 is associated with poor overall survival in patients with diffuse large B-cell lymphoma. Blood 126(19):2193–2201. https://doi.org/10.1182/blood-2015-02-629600

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Chen BJ, Chapuy B, Ouyang J, Sun HH, Roemer MG, Xu ML, Yu H, Fletcher CD, Freeman GJ, Shipp MA, Rodig SJ (2013) PD-L1 expression is characteristic of a subset of aggressive B-cell lymphomas and virus-associated malignancies. Clin Cancer Res 19(13):3462–3473. https://doi.org/10.1158/1078-0432.ccr-13-0855

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Miyoshi H, Kiyasu J, Kato T, Yoshida N, Shimono J, Yokoyama S, Taniguchi H, Sasaki Y, Kurita D, Kawamoto K, Kato K, Imaizumi Y, Seto M, Ohshima K (2016) PD-L1 expression on neoplastic or stromal cells is respectively a poor or good prognostic factor for adult T-cell leukemia/lymphoma. Blood 128(10):1374–1381. https://doi.org/10.1182/blood-2016-02-698936

    Article  CAS  PubMed  Google Scholar 

  33. Vranic S, Ghosh N, Kimbrough J, Bilalovic N, Bender R, Arguello D, Veloso Y, Dizdarevic A, Gatalica Z (2016) PD-L1 status in refractory lymphomas. PLoS ONE 11(11):e0166266. https://doi.org/10.1371/journal.pone.0166266

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Andorsky DJ, Yamada RE, Said J, Pinkus GS, Betting DJ, Timmerman JM (2011) Programmed death ligand 1 is expressed by non-hodgkin lymphomas and inhibits the activity of tumor-associated T cells. Clin Cancer Res 17(13):4232–4244. https://doi.org/10.1158/1078-0432.ccr-10-2660

    Article  CAS  PubMed  Google Scholar 

  35. Hatogai K, Kitano S, Fujii S, Kojima T, Daiko H, Nomura S, Yoshino T, Ohtsu A, Takiguchi Y, Doi T, Ochiai A (2016) Comprehensive immunohistochemical analysis of tumor microenvironment immune status in esophageal squamous cell carcinoma. Oncotarget 7(30):47252–47264. https://doi.org/10.18632/oncotarget.10055

    Article  PubMed  PubMed Central  Google Scholar 

  36. Yu H, Yang J, Jiao S, Li Y, Zhang W, Wang J (2015) Cytotoxic T lymphocyte antigen 4 expression in human breast cancer: implications for prognosis. Cancer Immunol Immunother 64(7):853–860. https://doi.org/10.1007/s00262-015-1696-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE, Chow LQ, Vokes EE, Felip E, Holgado E, Barlesi F, Kohlhaufl M, Arrieta O, Burgio MA, Fayette J, Lena H, Poddubskaya E, Gerber DE, Gettinger SN, Rudin CM, Rizvi N, Crino L, Blumenschein GR Jr, Antonia SJ, Dorange C, Harbison CT, Graf Finckenstein F, Brahmer JR (2015) Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med 373(17):1627–1639. https://doi.org/10.1056/NEJMoa1507643

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Brahmer J, Reckamp KL, Baas P, Crino L, Eberhardt WE, Poddubskaya E, Antonia S, Pluzanski A, Vokes EE, Holgado E, Waterhouse D, Ready N, Gainor J, Aren Frontera O, Havel L, Steins M, Garassino MC, Aerts JG, Domine M, Paz-Ares L, Reck M, Baudelet C, Harbison CT, Lestini B, Spigel DR (2015) Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med 373(2):123–135. https://doi.org/10.1056/NEJMoa1504627

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Herbst RS, Baas P, Kim DW, Felip E, Perez-Gracia JL, Han JY, Molina J, Kim JH, Arvis CD, Ahn MJ, Majem M, Fidler MJ, de Castro G, Jr., Garrido M, Lubiniecki GM, Shentu Y, Im E, Dolled-Filhart M, Garon EB, (2016) Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet 387(10027):1540–1550. https://doi.org/10.1016/s0140-6736(15)01281-7

    Article  CAS  PubMed  Google Scholar 

  40. Younes A, Santoro A, Shipp M, Zinzani PL, Timmerman JM, Ansell S, Armand P, Fanale M, Ratanatharathorn V, Kuruvilla J, Cohen JB, Collins G, Savage KJ, Trneny M, Kato K, Farsaci B, Parker SM, Rodig S, Roemer MG, Ligon AH, Engert A (2016) Nivolumab for classical Hodgkin’s lymphoma after failure of both autologous stem-cell transplantation and brentuximab vedotin: a multicentre, multicohort, single-arm phase 2 trial. Lancet Oncol 17(9):1283–1294. https://doi.org/10.1016/s1470-2045(16)30167-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Takeuchi M, Miyoshi H, Nakashima K, Kawamoto K, Yamada K, Yanagida E, Muta H, Moritsubo M, Umeno T, Suzuki T, Seto M, Ohshima K (2020) Comprehensive immunohistochemical analysis of immune checkpoint molecules in adult T cell leukemia/lymphoma. Ann Hematol 99(5):1093–1098. https://doi.org/10.1007/s00277-020-03967-x

    Article  CAS  PubMed  Google Scholar 

  42. Kanda Y (2013) Investigation of the freely available easy-to-use software “EZR” for medical statistics. Bone Marrow Transplant 48(3):452–458. https://doi.org/10.1038/bmt.2012.244

    Article  CAS  PubMed  Google Scholar 

  43. Ramsay AG, Clear AJ, Fatah R, Gribben JG (2012) Multiple inhibitory ligands induce impaired T-cell immunologic synapse function in chronic lymphocytic leukemia that can be blocked with lenalidomide: establishing a reversible immune evasion mechanism in human cancer. Blood 120(7):1412–1421. https://doi.org/10.1182/blood-2012-02-411678

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Alsaab HO, Sau S, Alzhrani R, Tatiparti K, Bhise K, Kashaw SK, Iyer AK (2017) PD-1 and PD-L1 Checkpoint Signaling Inhibition for Cancer Immunotherapy: Mechanism, Combinations, and Clinical Outcome. Front Pharmacol 8:561. https://doi.org/10.3389/fphar.2017.00561

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Kataoka K, Iwanaga M, Yasunaga JI, Nagata Y, Kitanaka A, Kameda T, Yoshimitsu M, Shiraishi Y, Sato-Otsubo A, Sanada M, Chiba K, Tanaka H, Ochi Y, Aoki K, Suzuki H, Shiozawa Y, Yoshizato T, Sato Y, Yoshida K, Nosaka K, Hishizawa M, Itonaga H, Imaizumi Y, Munakata W, Shide K, Kubuki Y, Hidaka T, Nakamaki T, Ishiyama K, Miyawaki S, Ishii R, Nureki O, Tobinai K, Miyazaki Y, Takaori-Kondo A, Shibata T, Miyano S, Ishitsuka K, Utsunomiya A, Shimoda K, Matsuoka M, Watanabe T, Ogawa S (2017) Prognostic relevance of integrated genetic profiling in adult T-cell leukemia/lymphoma. Blood. https://doi.org/10.1182/blood-2017-01-761874

    Article  PubMed  PubMed Central  Google Scholar 

  46. Ratner L, Waldmann TA, Janakiram M, Brammer JE (2018) Rapid Progression of Adult T-Cell Leukemia-Lymphoma after PD-1 Inhibitor Therapy. N Engl J Med 378(20):1947–1948. https://doi.org/10.1056/NEJMc1803181

    Article  PubMed  Google Scholar 

  47. Rauch DA, Conlon KC, Janakiram M, Brammer JE, Harding JC, Ye BH, Zang X, Ren X, Olson S, Cheng X, Miljkovic MD, Sundaramoorthi H, Joseph A, Skidmore ZL, Griffith O, Griffith M, Waldmann TA, Ratner L (2019) Rapid progression of adult T-cell leukemia/lymphoma as tumor-infiltrating Tregs after PD-1 blockade. Blood 134(17):1406–1414. https://doi.org/10.1182/blood.2019002038

    Article  PubMed  PubMed Central  Google Scholar 

  48. Yasuma K, Yasunaga J, Takemoto K, Sugata K, Mitobe Y, Takenouchi N, Nakagawa M, Suzuki Y, Matsuoka M (2016) HTLV-1 bZIP factor impairs anti-viral immunity by inducing co-inhibitory molecule, T cell immunoglobulin and ITIM domain (TIGIT). PLoS Pathog 12(1):e1005372. https://doi.org/10.1371/journal.ppat.1005372

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Querfeld C, Wu X, Stiller T, et al (2019) Phase 1 Results of Anti-PD-Ligand 1 (Durvalumab) & Lenalidomide in Patients with Cutaneous T Cell Lymphoma and Correlation with Programmed Death Ligand 1 Expression and Gene Expression Profile[abstract]. 61th ASH Annual Meeting. Abstract 4024

Download references

Acknowledgements

The authors thank the medical, nursing, data processing, laboratory, and clinical staff members at the participating centers for their important contribution to this study and their dedicated patient care.

Funding

This work was supported by a grant from the Practical Research for Innovative Cancer Control program of the Japan Agency for Medical Research and Development (19ck0106342h0003).

Author information

Authors and Affiliations

  1. Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan

    Akio Onishi, Kinuko Tajima, Junko Yamaguchi, Ichiro Kawashima, Akihisa Kawajiri, Tomonari Takemura, Ayumu Ito, Takashi Tanaka, Keiji Okinaka, Yoshihiro Inamoto, Saiko Kurosawa, Sung-Won Kim & Takahiro Fukuda

  2. Department of Hematology, Matsushita Memorial Hospital, Osaka, Japan

    Akio Onishi

  3. Department of Hematology, Osaka International Cancer Institute, 3-1-69, Otemae, Chuo-Ku, Osaka, 541-8567, Japan

    Shigeo Fuji

  4. Department of Experimental Therapeutics, Exploratory Oncology Research, National Cancer Center Hospital, Tokyo, Japan

    Shigehisa Kitano

  5. Department of Pathology, National Cancer Center Hospital, Tokyo, Japan

    Akiko Miyagi Maeshima

  6. Department of Hematology, National Cancer Center Hospital, Tokyo, Japan

    Wataru Munakata, Dai Maruyama & Kensei Tobinai

Authors
  1. Akio Onishi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shigeo Fuji
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shigehisa Kitano
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Akiko Miyagi Maeshima
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kinuko Tajima
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Junko Yamaguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ichiro Kawashima
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Akihisa Kawajiri
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Tomonari Takemura
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Ayumu Ito
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Takashi Tanaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Keiji Okinaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Yoshihiro Inamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Saiko Kurosawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Sung-Won Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Wataru Munakata
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Dai Maruyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Kensei Tobinai
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Takahiro Fukuda
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Shigeo Fuji.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher's note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 1441 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Onishi, A., Fuji, S., Kitano, S. et al. Prognostic implication of CTLA-4, PD-1, and PD-L1 expression in aggressive adult T-cell leukemia–lymphoma. Ann Hematol 101, 799–810 (2022). https://doi.org/10.1007/s00277-022-04760-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00277-022-04760-8

Keywords

Search

Navigation