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CXCL9-modified CAR T cells improve immune cell infiltration and antitumor efficacy

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Abstract

Chimeric antigen receptor (CAR) T cells remain unsatisfactory in treating solid tumors. The frequency of tumor-infiltrating T cells is closely related to the good prognosis of patients. Augmenting T cell accumulation in the tumor microenvironment is essential for tumor clearance. To overcome insufficient immune cell infiltration, innovative CAR designs need to be developed immediately. CXCL9 plays a pivotal role in regulating T cell migration and inhibiting tumor angiogenesis. Therefore, we engineered CAR T cells expressing CXCL9 (CART-CXCL9). The addition of CXCL9 enhanced cytokine secretion and cytotoxicity of CAR T cells and endowed CAR T cells with the ability to recruit activated T cells and antiangiogenic effect. In tumor-bearing mice, CART-CXCL9 cells attracted more T cell trafficking to the tumor site and inhibited angiogenesis than conventional CAR T cells. Additionally, CART-CXCL9 cell therapy slowed tumor growth and prolonged mouse survival, displaying superior antitumor activity. Briefly, modifying CAR T cells to express CXCL9 could effectively improve CAR T cell efficacy against solid tumors.

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Data availability

The datasets used in this study are available from the corresponding author on reasonable request.

References

  1. Maude SL, Laetsch TW, Buechner J, Rives S, Boyer M, Bittencourt H, Bader P, Verneris MR, Stefanski HE, Myers GD, Qayed M, De Moerloose B, Hiramatsu H, Schlis K, Davis KL, Martin PL, Nemecek ER, Yanik GA, Peters C et al (2018) Tisagenlecleucel in children and young adults with B-Cell lymphoblastic leukemia. N Engl J Med 378(5):439–448. https://doi.org/10.1056/NEJMoa1709866

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Park JH, Rivière I, Gonen M, Wang X, Sénéchal B, Curran KJ, Sauter C, Wang Y, Santomasso B, Mead E, Roshal M, Maslak P, Davila M, Brentjens RJ, Sadelain M (2018) Long-term follow-up of CD19 CAR therapy in acute lymphoblastic leukemia. N Engl J Med 378(5):449–459. https://doi.org/10.1056/NEJMoa1709919

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Zhang Z, Liu S, Zhang B, Qiao L, Zhang Y, Zhang Y (2020) T cell dysfunction and exhaustion in cancer. Front Cell Dev Biol. https://doi.org/10.3389/fcell.2020.00017

    Article  PubMed  PubMed Central  Google Scholar 

  4. Qu J, Mei Q, Chen L, Zhou J (2021) Chimeric antigen receptor (CAR)-T-cell therapy in non-small-cell lung cancer (NSCLC): current status and future perspectives. Cancer Immunol Immunother 70(3):619–631. https://doi.org/10.1007/s00262-020-02735-0

    Article  CAS  PubMed  Google Scholar 

  5. Tian Y, Li Y, Shao Y, Zhang Y (2020) Gene modification strategies for next-generation CAR T cells against solid cancers. J Hematol Oncol. https://doi.org/10.1186/s13045-020-00890-6

    Article  PubMed  PubMed Central  Google Scholar 

  6. Liu G, Rui W, Zheng H, Huang D, Yu F, Zhang Y, Dong J, Zhao X, Lin X (2020) CXCR2-modified CAR-T cells have enhanced trafficking ability that improves treatment of hepatocellular carcinoma. Eur J Immunol 50(5):712–724. https://doi.org/10.1002/eji.201948457

    Article  CAS  PubMed  Google Scholar 

  7. Jena B, Dotti G, Cooper LJN (2010) Redirecting T-cell specificity by introducing a tumor-specific chimeric antigen receptor. Blood 116(7):1035–1044. https://doi.org/10.1182/blood-2010-01-043737

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Dangaj D, Bruand M, Grimm AJ, Ronet C, Barras D, Duttagupta PA, Lanitis E, Duraiswamy J, Tanyi JL, Benencia F, Conejo-Garcia J, Ramay HR, Montone KT, Powell DJ, Gimotty PA, Facciabene A, Jackson DG, Weber JS, Rodig SJ et al (2019) Cooperation between constitutive and inducible chemokines enables T Cell engraftment and immune attack in solid tumors. Cancer Cell 35(6):885–900. https://doi.org/10.1016/j.ccell.2019.05.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Tokunaga R, Zhang W, Naseem M, Puccini A, Berger MD, Soni S, McSkane M, Baba H, Lenz H-J (2018) CXCL9, CXCL10, CXCL11/CXCR3 axis for immune activation – a target for novel cancer therapy. Cancer Treat Rev 63:40–47. https://doi.org/10.1016/j.ctrv.2017.11.007

    Article  CAS  PubMed  Google Scholar 

  10. Nazari A, Ahmadi Z, Hassanshahi G, Abbasifard M, Taghipour Z, Falahati-pour SK, Khorramdelazad H (2020) Effective treatments for bladder cancer affecting CXCL9/CXCL10/CXCL11/CXCR3 axis: a review. Oman Med J 35(2):e103–e103. https://doi.org/10.5001/omj.2020.21

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Mauldin IS, Wages NA, Stowman AM, Wang E, Smolkin ME, Olson WC, Deacon DH, Smith KT, Galeassi NV, Chianese-Bullock KA, Dengel LT, Marincola FM, Petroni GR, Mullins DW, Slingluff CL Jr (2016) Intratumoral interferon-gamma increases chemokine production but fails to increase T cell infiltration of human melanoma metastases. Cancer Immunol Immunother 65(10):1189–1199. https://doi.org/10.1007/s00262-016-1881-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Ouedraogo DE, Makinson A, Kuster N, Nagot N, Rubbo PA, Bollore K, Foulongne V, Cartron G, Olive D, Reynes J, Vendrell JP, Tuaillon E (2013) Increased T-cell activation and Th1 cytokine concentrations prior to the diagnosis of B-cell lymphoma in HIV infected patients. J Clin Immunol 33(1):22–29. https://doi.org/10.1007/s10875-012-9766-0

    Article  CAS  PubMed  Google Scholar 

  13. Mosser DM, Edwards JP (2008) Exploring the full spectrum of macrophage activation. Nat Rev Immunol 8(12):958–969. https://doi.org/10.1038/nri2448

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Zohar Y, Wildbaum G, Novak R, Salzman AL, Thelen M, Alon R, Barsheshet Y, Karp CL, Karin N (2014) CXCL11-dependent induction of FOXP3-negative regulatory T cells suppresses autoimmune encephalomyelitis. J Clin Investig 124(5):2009–2022. https://doi.org/10.1172/jci71951

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Huang Y, Kim BYS, Chan CK, Hahn SM, Weissman IL, Jiang W (2018) Improving immune–vascular crosstalk for cancer immunotherapy. Nat Rev Immunol 18(3):195–203. https://doi.org/10.1038/nri.2017.145

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Chow MT, Ozga AJ, Servis RL, Frederick DT, Lo JA, Fisher DE, Freeman GJ, Boland GM, Luster AD (2019) Intratumoral activity of the CXCR3 chemokine system is required for the efficacy of anti-PD-1 therapy. Immunity 50(6):1498–1512. https://doi.org/10.1016/j.immuni.2019.04.010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Cao Y, Huang H, Wang Z, Zhang G (2017) The inflammatory CXC chemokines, GROαhigh, IP-10low, and MIGlow, in tumor microenvironment can be used as new indicators for non-small cell lung cancer progression. Immunol Invest 46(4):361–374. https://doi.org/10.1080/08820139.2017.1280052

    Article  CAS  PubMed  Google Scholar 

  18. Wu Z, Huang X, Han X, Li Z, Zhu Q, Yan J, Yu S, Jin Z, Wang Z, Zheng Q, Wang Y (2016) The chemokine CXCL9 expression is associated with better prognosis for colorectal carcinoma patients. Biomed Pharmacother 78:8–13. https://doi.org/10.1016/j.biopha.2015.12.021

    Article  CAS  PubMed  Google Scholar 

  19. Ding Q, Lu P, Xia Y, Ding S, Fan Y, Li X, Han P, Liu J, Tian D, Liu M (2016) CXCL9: evidence and contradictions for its role in tumor progression. Cancer Med 5(11):3246–3259. https://doi.org/10.1002/cam4.934

    Article  PubMed  PubMed Central  Google Scholar 

  20. Walser TC, Ma X, Kundu N, Dorsey R, Goloubeva O, Fulton AM (2007) Immune-mediated modulation of breast cancer growth and metastasis by the chemokine mig (CXCL9) in a murine model. J Immunother 30(5):490–498. https://doi.org/10.1097/CJI.0b013e318031b551

    Article  CAS  PubMed  Google Scholar 

  21. Du J, Su S, Li H, Shao J, Meng F, Yang M, Qian H, Zou Z, Qian X, Liu B (2017) Low dose irradiation increases adoptive cytotoxic T lymphocyte migration in gastric cancer. Exp Ther Med. https://doi.org/10.3892/etm.2017.5305

    Article  PubMed  PubMed Central  Google Scholar 

  22. Han X, Wang Y, Sun J, Tan T, Cai X, Lin P, Tan Y, Zheng B, Wang B, Wang J, Xu L, Yu Z, Xu Q, Wu X, Gu Y (2019) Role of CXCR3 signaling in response to anti-PD-1 therapy. EBioMedicine 48:169–177. https://doi.org/10.1016/j.ebiom.2019.08.067

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Yin P, Gui L, Wang C, Yan J, Liu M, Ji L, Wang Y, Ma B, Gao WQ (2020) Targeted delivery of CXCL9 and OX40L by mesenchymal stem cells elicits potent antitumor immunity. Mol Ther 28(12):2553–2563. https://doi.org/10.1016/j.ymthe.2020.08.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Lai Y, Weng J, Wei X, Qin L, Lai P, Zhao R, Jiang Z, Li B, Lin S, Wang S, Wu Q, Tang Z, Liu P, Pei D, Yao Y, Du X, Li P (2017) Toll-like receptor 2 costimulation potentiates the antitumor efficacy of CAR T Cells. Leukemia 32(3):801–808. https://doi.org/10.1038/leu.2017.249

    Article  CAS  PubMed  Google Scholar 

  25. Mei Z, Zhang K, Lam AKY, Huang J, Qiu F, Qiao B, Zhang Y (2019) MUC1 as a target for CAR-T therapy in head and neck squamous cell carinoma. Cancer Med 9(2):640–652. https://doi.org/10.1002/cam4.2733

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Liu JY, Li F, Wang LP, Chen XF, Wang D, Cao L, Ping Y, Zhao S, Li B, Thorne SH, Zhang B, Kalinski P, Zhang Y (2015) CTL- vs Treg lymphocyte-attracting chemokines, CCL4 and CCL20, are strong reciprocal predictive markers for survival of patients with oesophageal squamous cell carcinoma. Br J Cancer 113(5):747–755. https://doi.org/10.1038/bjc.2015.290

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Karin N, Wildbaum G, Thelen M (2016) Biased signaling pathways via CXCR3 control the development and function of CD4 + T cell subsets. J Leukoc Biol 99(6):857–862. https://doi.org/10.1189/jlb.2MR0915-441R

    Article  CAS  PubMed  Google Scholar 

  28. Nör JE, Christensen J, Liu J, Peters M, Mooney DJ, Strieter RM, Polverini PJ (2001) Up-regulation of Bcl-2 in microvascular endothelial cells enhances intratumoral angiogenesis and accelerates tumor growth. Cancer Res 61(5):2183–2188

    PubMed  Google Scholar 

  29. Rafiq S, Hackett CS, Brentjens RJ (2019) Engineering strategies to overcome the current roadblocks in CAR T cell therapy. Nat Rev Clin Oncol 17(3):147–167. https://doi.org/10.1038/s41571-019-0297-y

    Article  PubMed  PubMed Central  Google Scholar 

  30. Depil S, Duchateau P, Grupp SA, Mufti G, Poirot L (2020) ‘Off-the-shelf’ allogeneic CAR T cells: development and challenges. Nat Rev Drug Discovery 19(3):185–199. https://doi.org/10.1038/s41573-019-0051-2

    Article  CAS  PubMed  Google Scholar 

  31. Barnes TA, Amir E (2017) HYPE or HOPE: the prognostic value of infiltrating immune cells in cancer. Br J Cancer 117(4):451–460

    Article  CAS  Google Scholar 

  32. Wang D, Yu W, Lian J, Wu Q, Liu S, Yang L, Li F, Huang L, Chen X, Zhang Z, Li A, Liu J, Sun Z, Wang J, Yuan W, Zhang Y (2020) Th17 cells inhibit CD8 + T cell migration by systematically downregulating CXCR3 expression via IL-17A/STAT3 in advanced-stage colorectal cancer patients. J Hematol Oncol. https://doi.org/10.1186/s13045-020-00897-z

    Article  PubMed  PubMed Central  Google Scholar 

  33. Jin L, Tao H, Karachi A, Long Y, Hou AY, Na M, Dyson KA, Grippin AJ, Deleyrolle LP, Zhang W, Rajon DA, Wang QJ, Yang JC, Kresak JL, Sayour EJ, Rahman M, Bova FJ, Lin Z, Mitchell DA et al (2019) CXCR1- or CXCR2-modified CAR T cells co-opt IL-8 for maximal antitumor efficacy in solid tumors. Nat Commun. https://doi.org/10.1038/s41467-019-11869-4

    Article  PubMed  PubMed Central  Google Scholar 

  34. Lin Y, Yin H, An H, Zhou C, Zhou L, Chen S, McGowan E (2019) Chemokine receptor CCR2b expressing anti-Tn-MUC1 CAR-T cells enhanced anti-breast cancer activity. Ann Oncol 30:xi12. https://doi.org/10.1093/annonc/mdz448.002

    Article  Google Scholar 

  35. Adachi K, Kano Y, Nagai T, Okuyama N, Sakoda Y, Tamada K (2018) IL-7 and CCL19 expression in CAR-T cells improves immune cell infiltration and CAR-T cell survival in the tumor. Nat Biotechnol 36(4):346–351. https://doi.org/10.1038/nbt.4086

    Article  CAS  PubMed  Google Scholar 

  36. Spranger S, Dai D, Horton B, Gajewski TF (2017) Tumor-residing bat f3 dendritic cells are required for effector T cell trafficking and adoptive T cell therapy. Cancer Cell 31(5):711–723. https://doi.org/10.1016/j.ccell.2017.04.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Moon EK, Wang LS, Bekdache K, Lynn RC, Lo A, Thorne SH, Albelda SM (2018) Intra-tumoral delivery of CXCL11 via a vaccinia virus, but not by modified T cells, enhances the efficacy of adoptive T cell therapy and vaccines. Oncoimmunology 7(3):e1395997. https://doi.org/10.1080/2162402X.2017.1395997

    Article  PubMed  PubMed Central  Google Scholar 

  38. Xia M, Chen J, Meng G, Shen H, Dong J (2021) CXCL10 encoding synNotch T cells enhance anti-tumor immune responses without systemic side effect. Biochem Biophys Res Commun 534:765–772. https://doi.org/10.1016/j.bbrc.2020.11.002

    Article  CAS  PubMed  Google Scholar 

  39. Karin N, Wildbaum G, Thelen M (2016) Biased signaling pathways via CXCR3 control the development and function of CD4 + T cell subsets. J Leukoc Biol 99(6):857–862. https://doi.org/10.1189/jlb.2MR0915-441R

    Article  CAS  PubMed  Google Scholar 

  40. Chen Y, Xu J, Wu X, Yao H, Yan Z, Guo T, Wang W, Wang P, Li Y, Yang X, Li H, Bian H, Chen Z-N (2020) CD147 regulates antitumor CD8 + T-cell responses to facilitate tumor-immune escape. Cell Mol Immunol. https://doi.org/10.1038/s41423-020-00570-y

    Article  PubMed  PubMed Central  Google Scholar 

  41. Meng Z, Ren D, Zhang K, Zhao J, Jin X, Wu H (2020) Using estimate algorithm to establish an 8-mRNA signature prognosis prediction system and identify immunocyte infiltration-related genes in pancreatic adenocarcinoma. Aging 12(6):5048–5070. https://doi.org/10.18632/aging.102931

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Tokunaga R, Zhang W, Naseem M, Puccini A, Berger MD, Soni S, McSkane M, Baba H, Lenz HJ (2018) CXCL9, CXCL10, CXCL11/CXCR3 axis for immune activation - a target for novel cancer therapy. Cancer Treat Rev 63:40–47. https://doi.org/10.1016/j.ctrv.2017.11.007

    Article  CAS  PubMed  Google Scholar 

  43. Yu L, Yang X, Xu C, Sun J, Fang Z, Pan H, Han W (2020) Comprehensive analysis of the expression and prognostic value of CXC chemokines in colorectal cancer. Int Immunopharmacol 89:107077. https://doi.org/10.1016/j.intimp.2020.107077

    Article  CAS  PubMed  Google Scholar 

  44. Zhang K, Zhang L, Mi Y, Tang Y, Ren F, Liu B, Zhang Y, Zheng P (2020) A ceRNA network and a potential regulatory axis in gastric cancer with different degrees of immune cell infiltration. Cancer Sci 111(11):4041–4050. https://doi.org/10.1111/cas.14634

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Huang B, Han W, Sheng Z-F, Shen G-L (2020) Identification of immune-related biomarkers associated with tumorigenesis and prognosis in cutaneous melanoma patients. Cancer Cell Int. https://doi.org/10.1186/s12935-020-01271-2

    Article  PubMed  PubMed Central  Google Scholar 

  46. Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ, He J (2016) Cancer statistics in China, 2015. CA A Cancer J Clin 66(2):115–132. https://doi.org/10.3322/caac.21338

    Article  Google Scholar 

  47. Morello A, Sadelain M, Adusumilli PS (2015) Mesothelin-targeted CARs: driving T cells to solid tumors. Cancer Discov 6(2):133–146. https://doi.org/10.1158/2159-8290.cd-15-0583

    Article  PubMed  PubMed Central  Google Scholar 

  48. Groom Joanna R, Richmond J, Murooka Thomas T, Sorensen Elizabeth W, Sung Jung H, Bankert K, von Andrian UH, Moon James J, Mempel Thorsten R, Luster AD (2012) CXCR3 chemokine receptor-ligand interactions in the lymph node optimize CD4 + T helper 1 cell differentiation. Immunity 37(6):1091–1103. https://doi.org/10.1016/j.immuni.2012.08.016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Ager A, Watson HA, Wehenkel SC, Mohammed RN (2016) Homing to solid cancers: a vascular checkpoint in adoptive cell therapy using CAR T-cells. Biochem Soc Trans 44(2):377–385. https://doi.org/10.1042/bst20150254

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Hong M, Puaux A-L, Huang C, Loumagne L, Tow C, Mackay C, Kato M, Prévost-Blondel A, Avril M-F, Nardin A, Abastado J-P (2011) Chemotherapy induces intratumoral expression of chemokines in cutaneous melanoma, favoring T-cell infiltration and tumor control. Cancer Res 71(22):6997–7009. https://doi.org/10.1158/0008-5472.Can-11-1466

    Article  CAS  PubMed  Google Scholar 

  51. Gudowska-Sawczuk M, Kudelski J, Mroczko B (2020) The role of chemokine receptor CXCR3 and its ligands in renal cell carcinoma. Int J Mol Sci 21(22):8582. https://doi.org/10.3390/ijms21228582

    Article  CAS  PubMed Central  Google Scholar 

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Acknowledgements

We would like to thank Editage for English language editing and the staff and students of the Biotherapy Center at the First Affiliated Hospital of Zhengzhou University for their valuable help in this study.

Funding

This work was supported by grants from the National Natural Science Foundation of China (81771781), National Science and Technology Major Project of China (2020ZX09201-009), Program of the Major Research Plan of the National Natural Science Foundation of China (91942314), and Major public welfare projects in Henan Province (201300310400), and National Natural Science Foundation of China General Program (81872333).

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  1. Yonggui Tian, Chunli Wen, Zhen Zhang and Yanfen Liu contributed equally to this work.

Authors and Affiliations

  1. Biotherapy Center and Cancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China

    Yonggui Tian, Chunli Wen, Zhen Zhang, Yanfen Liu, Feng Li, Qitai Zhao, Chang Yao, Kaiyuan Ni, Shengli Yang & Yi Zhang

  2. State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou University, Zhengzhou, 450052, Henan, China

    Yonggui Tian, Chunli Wen, Zhen Zhang, Yanfen Liu, Feng Li, Qitai Zhao, Chang Yao, Kaiyuan Ni, Shengli Yang & Yi Zhang

  3. Henan Key Laboratory for Tumor Immunology and Biotherapy, Zhengzhou, 450052, Henan, China

    Yonggui Tian, Chunli Wen, Zhen Zhang, Yanfen Liu, Feng Li, Qitai Zhao, Chang Yao, Kaiyuan Ni, Shengli Yang & Yi Zhang

  4. School of Life Sciences, Zhengzhou University, Zhengzhou, 450052, Henan, China

    Chunli Wen & Yi Zhang

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Contributions

YZ and SY designed and supervised the study. YT, CW, ZZ and YL performed the experiments. FL, QZ, CY, and KN helped to complete the experiment. All authors read and approved the final manuscript.

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Correspondence to Shengli Yang or Yi Zhang.

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Tian, Y., Wen, C., Zhang, Z. et al. CXCL9-modified CAR T cells improve immune cell infiltration and antitumor efficacy. Cancer Immunol Immunother 71, 2663–2675 (2022). https://doi.org/10.1007/s00262-022-03193-6

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