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Open Access 01-05-2024 | Radiotherapy | Research

IL7 in combination with radiotherapy stimulates a memory T-cell response to improve outcomes in HNSCC models

Authors: Justin Yu, Jacob Gadwa, Richard B. Ross, Michael Knitz, Laurel B. Darragh, Khalid N. M. Abdelazeem, Jessica Beynor, Brooke Neupert, Alexander Nguyen, Diemmy Nguyen, Nicholas Olimpo, Sophia Corbo, Benjamin Van Court, Angelo D’Alessandro, Anthony Saviola, Sana D. Karam

Published in: Cancer Immunology, Immunotherapy | Issue 5/2024

Abstract

Clinically approved head and neck squamous cell carcinoma (HNSCC) immunotherapies manipulate the immune checkpoint blockade (ICB) axis but have had limited success outside of recurrent/metastatic disease. Interleukin-7 (IL7) has been shown to be essential for effector T-cell survival, activation, and proliferation. Here, we show that IL7 in combination with radiotherapy (RT) is effective in activating CD8 + T-cells for reducing tumor growth. Our studies were conducted using both human papillomavirus related and unrelated orthotopic HNSCC murine models. Immune populations from the tumor, draining lymph nodes, and blood were compared between treatment groups and controls using flow cytometry, proteomics, immunofluorescence staining, and RNA sequencing. Treatment with RT and IL7 (RT + IL7) resulted in significant tumor growth reduction, high CD8 T-cell tumor infiltration, and increased proliferation of T-cell progenitors in the bone marrow. IL7 also expanded a memory-like subpopulation of CD8 T-cells. These results indicate that IL7 in combination with RT can serve as an effective immunotherapy strategy outside of the conventional ICB axis to drive the antitumor activity of CD8 T-cells.

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Ferlay J, Colombet M, Soerjomataram I et al (2019) Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods. Int J cancer 144(8):1941–1953. https://doi.org/10.1002/ijc.31937CrossRefPubMed

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68(6):394–424. https://doi.org/10.3322/caac.21492CrossRefPubMed

Johnson DE, Burtness B, Leemans CR, Lui VWY, Bauman JE, Grandis JR (2020) Head and neck squamous cell carcinoma. Nat Rev Dis Prim 6(1):92. https://doi.org/10.1038/s41572-020-00224-3CrossRefPubMed

Mandal R, Şenbabaoğlu Y, Desrichard A et al (2016) The head and neck cancer immune landscape and its immunotherapeutic implications. JCI insight 1(17):e89829. https://doi.org/10.1172/jci.insight.89829CrossRefPubMedPubMedCentral

Blot WJ, McLaughlin JK, Winn DM et al (1988) Smoking and drinking in relation to oral and pharyngeal cancer. Cancer Res 48(11):3282–3287PubMed

Talamini R, Bosetti C, La Vecchia C et al (2002) Combined effect of tobacco and alcohol on laryngeal cancer risk: a case-control study. Cancer Causes Control 13(10):957–964. https://doi.org/10.1023/a:1021944123914CrossRefPubMed

Stein AP, Saha S, Kraninger JL et al (2015) Prevalence of human papillomavirus in oropharyngeal cancer: a systematic review. Cancer J 21(3):138–146. https://doi.org/10.1097/PPO.0000000000000115CrossRefPubMedPubMedCentral

Isayeva T, Li Y, Maswahu D, Brandwein-Gensler M (2012) Human papillomavirus in non-oropharyngeal head and neck cancers: a systematic literature review. Head Neck Pathol 6(Suppl 1):S104-20. https://doi.org/10.1007/s12105-012-0368-1CrossRefPubMed

Arina A, Gutiontov SI, Weichselbaum RR (2020) Radiotherapy and immunotherapy for cancer: from “systemic” to “multisite.” Clin Cancer Res 26(12):2777–2782. https://doi.org/10.1158/1078-0432.CCR-19-2034CrossRefPubMedPubMedCentral

10.

Twomey JD, Zhang B (2021) Cancer immunotherapy update: FDA-approved checkpoint inhibitors and companion diagnostics. AAPS J 23(2):39. https://doi.org/10.1208/s12248-021-00574-0CrossRefPubMed

11.

Liu X, Guo C-Y, Tou F-F et al (2020) Association of PD-L1 expression status with the efficacy of PD-1/PD-L1 inhibitors and overall survival in solid tumours: A systematic review and meta-analysis. Int J cancer 147(1):116–127. https://doi.org/10.1002/ijc.32744CrossRefPubMed

12.

Hodi FS, O’Day SJ, McDermott DF et al (2010) Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 363(8):711–723. https://doi.org/10.1056/NEJMoa1003466CrossRefPubMedPubMedCentral

13.

Davis AA, Patel VG (2019) The role of PD-L1 expression as a predictive biomarker: an analysis of all US food and drug administration (FDA) approvals of immune checkpoint inhibitors. J Immunother cancer 7(1):278. https://doi.org/10.1186/s40425-019-0768-9CrossRefPubMedPubMedCentral

14.

Trivedi S, Sun L, Aggarwal C (2021) Immunotherapy for Head and Neck Cancer. Hematol Oncol Clin North Am 35(5):1021–1037. https://doi.org/10.1016/j.hoc.2021.05.010CrossRefPubMed

15.

Fasano M, Della CCM, Di Liello R et al (2022) Immunotherapy for head and neck cancer: present and future. Crit Rev Oncol Hematol 174:103679. https://doi.org/10.1016/j.critrevonc.2022.103679CrossRefPubMed

16.

Yu Y, Zakeri K, Lee N (2021) Javelin head neck 100: should we combine immunotherapy with radiation therapy? Oncotarget 12(21):2223–2226. https://doi.org/10.18632/oncotarget.27987CrossRefPubMedPubMedCentral

17.

Lee NY, Ferris RL, Psyrri A et al (2021) Avelumab plus standard-of-care chemoradiotherapy versus chemoradiotherapy alone in patients with locally advanced squamous cell carcinoma of the head and neck: a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial. Lancet Oncol 22(4):450–462. https://doi.org/10.1016/S1470-2045(20)30737-3CrossRefPubMed

18.

Machiels J-P, Tao Y, Burtness B et al (2020) Pembrolizumab given concomitantly with chemoradiation and as maintenance therapy for locally advanced head and neck squamous cell carcinoma: KEYNOTE-412. Future Oncol 16(18):1235–1243. https://doi.org/10.2217/fon-2020-0184CrossRefPubMed

19.

Winer H, Rodrigues GOL, Hixon JA et al (2022) IL-7: comprehensive review. Cytokine 160:156049. https://doi.org/10.1016/j.cyto.2022.156049CrossRefPubMed

20.

Schluns KS, Kieper WC, Jameson SC, Lefrançois L (2000) Interleukin-7 mediates the homeostasis of naïve and memory CD8 T cells in vivo. Nat Immunol 1(5):426–432. https://doi.org/10.1038/80868CrossRefPubMed

21.

Tan JT, Dudl E, LeRoy E et al (2001) IL-7 is critical for homeostatic proliferation and survival of naive T cells. Proc Natl Acad Sci U S A 98(15):8732–8737. https://doi.org/10.1073/pnas.161126098CrossRefPubMedPubMedCentral

22.

Geiselhart LA, Humphries CA, Gregorio TA, Mou S, Subleski J, Komschlies KL (2001) IL-7 administration alters the CD4:CD8 ratio, increases T cell numbers, and increases T cell function in the absence of activation. J Immunol 166(5):3019–3027. https://doi.org/10.4049/jimmunol.166.5.3019CrossRefPubMed

23.

Komschlies KL, Gregorio TA, Gruys ME, Back TC, Faltynek CR, Wiltrout RH (1994) Administration of recombinant human IL-7 to mice alters the composition of B-lineage cells and T cell subsets, enhances T cell function, and induces regression of established metastases. J Immunol. 152(12):5776–5784CrossRefPubMed

24.

Sportès C, Hakim FT, Memon SA et al (2008) Administration of rhIL-7 in humans increases in vivo TCR repertoire diversity by preferential expansion of naive T cell subsets. J Exp Med 205(7):1701–1714. https://doi.org/10.1084/jem.20071681CrossRefPubMedPubMedCentral

25.

Liu W, Putnam AL, Xu-Yu Z et al (2006) CD127 expression inversely correlates with FoxP3 and suppressive function of human CD4+ T reg cells. J Exp Med 203(7):1701–1711. https://doi.org/10.1084/jem.20060772CrossRefPubMedPubMedCentral

26.

Oweida A, Hararah MK, Phan A et al (2018) Resistance to radiotherapy and PD-L1 blockade is mediated by TIM-3 upregulation and regulatory T-cell infiltration. Clin Cancer Res 24(21):5368–5380. https://doi.org/10.1158/1078-0432.CCR-18-1038CrossRefPubMedPubMedCentral

27.

Darragh LB, Knitz MM, Hu J et al (2022) A phase I/Ib trial and biological correlate analysis of neoadjuvant SBRT with single-dose durvalumab in HPV-unrelated locally advanced HNSCC. Nat cancer 3(11):1300–1317. https://doi.org/10.1038/s43018-022-00450-6CrossRefPubMedPubMedCentral

28.

Sun D, Wang J, Han Y et al (2021) TISCH: a comprehensive web resource enabling interactive single-cell transcriptome visualization of tumor microenvironment. Nucleic Acids Res 49(D1):D1420–D1430. https://doi.org/10.1093/nar/gkaa1020CrossRefPubMed

29.

Cillo AR, Kürten CHL, Tabib T et al (2020) Immune landscape of viral- and carcinogen-driven head and neck cancer. Immunity 52(1):183-199.e9. https://doi.org/10.1016/j.immuni.2019.11.014CrossRefPubMedPubMedCentral

30.

Gadwa J, Amann M, Bickett TE et al (2023) Selective targeting of IL2Rβγ combined with radiotherapy triggers CD8- and NK-mediated immunity, abrogating metastasis in HNSCC. Cell reports Med 4(8):101150. https://doi.org/10.1016/j.xcrm.2023.101150CrossRef

31.

Oweida AJ, Darragh L, Phan A et al (2019) STAT3 modulation of regulatory T cells in response to radiation therapy in head and neck cancer. J Natl Cancer Inst 111(12):1339–1349. https://doi.org/10.1093/jnci/djz036CrossRefPubMedPubMedCentral

32.

Reschke R, Gajewski TF (2022) CXCL9 and CXCL10 bring the heat to tumors. Sci Immunol 7(73):eabq6509. https://doi.org/10.1126/sciimmunol.abq6509CrossRefPubMed

33.

Liu B, Zhang Y, Wang D, Hu X, Zhang Z (2022) Single-cell meta-analyses reveal responses of tumor-reactive CXCL13+ T cells to immune-checkpoint blockade. Nat cancer 3(9):1123–1136. https://doi.org/10.1038/s43018-022-00433-7CrossRefPubMed

34.

Karin N (2020) CXCR3 ligands in cancer and autoimmunity, chemoattraction of effector T cells, and beyond. Front Immunol 11:976. https://doi.org/10.3389/fimmu.2020.00976CrossRefPubMedPubMedCentral

35.

Sallusto F, Lenig D, Förster R, Lipp M, Lanzavecchia A (1999) Two subsets of memory T lymphocytes with distinct homing potentials and effector functions. Nature 401(6754):708–712. https://doi.org/10.1038/44385CrossRefPubMed

36.

Raud B, McGuire PJ, Jones RG, Sparwasser T, Berod L (2018) Fatty acid metabolism in CD8+ T cell memory: challenging current concepts. Immunol Rev 283(1):213–231. https://doi.org/10.1111/imr.12655CrossRefPubMedPubMedCentral

37.

Kipnis A, Irwin S, Izzo AA, Basaraba RJ, Orme IM (2005) Memory T lymphocytes generated by Mycobacterium bovis BCG vaccination reside within a CD4 CD44lo CD62 ligand(hi) population. Infect Immun 73(11):7759–7764. https://doi.org/10.1128/IAI.73.11.7759-7764.2005CrossRefPubMedPubMedCentral

38.

Rahim MK, Okholm TLH, Jones KB et al (2023) Dynamic CD8+ T cell responses to cancer immunotherapy in human regional lymph nodes are disrupted in metastatic lymph nodes. Cell 186(6):1127-1143.e18. https://doi.org/10.1016/j.cell.2023.02.021CrossRefPubMedPubMedCentral

39.

Plumb AW, Sheikh A, Carlow DA, Patton DT, Ziltener HJ, Abraham N (2017) Interleukin-7 in the transition of bone marrow progenitors to the thymus. Immunol Cell Biol 95(10):916–924. https://doi.org/10.1038/icb.2017.68CrossRefPubMed

40.

Knitz MW, Bickett TE, Darragh LB et al (2021) Targeting resistance to radiation-immunotherapy in cold HNSCCs by modulating the Treg-dendritic cell axis. J Immunother Cancer. https://doi.org/10.1136/jitc-2020-001955CrossRefPubMedPubMedCentral

41.

Darragh LB, Gadwa J, Pham TT et al (2022) Elective nodal irradiation mitigates local and systemic immunity generated by combination radiation and immunotherapy in head and neck tumors. Nat Commun 13(1):7015. https://doi.org/10.1038/s41467-022-34676-wCrossRefPubMedPubMedCentral

42.

Bickett TE, Knitz M, Darragh LB et al (2021) FLT3L Release by natural killer cells enhances response to radioimmunotherapy in preclinical models of HNSCC. Clin Cancer Res 27(22):6235–6249. https://doi.org/10.1158/1078-0432.CCR-21-0971CrossRefPubMedPubMedCentral

43.

Alfieri S, Cavalieri S, Licitra L (2018) Immunotherapy for recurrent/metastatic head and neck cancer. Curr Opin Otolaryngol Head Neck Surg 26(2):152–156. https://doi.org/10.1097/MOO.0000000000000448CrossRefPubMed

44.

Vallianou NG, Evangelopoulos A, Kounatidis D et al (2023) Immunotherapy in head and neck cancer: where do we stand? Curr Oncol Rep 25(8):897–912. https://doi.org/10.1007/s11912-023-01425-1CrossRefPubMed

45.

Bhatia A, Burtness B (2023) Treating head and neck cancer in the age of immunotherapy: a 2023 update. Drugs 83(3):217–248. https://doi.org/10.1007/s40265-023-01835-2CrossRefPubMed

46.

Cohen EEW, Bell RB, Bifulco CB et al (2019) The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of squamous cell carcinoma of the head and neck (HNSCC). J Immunother Cancer 7(1):184. https://doi.org/10.1186/s40425-019-0662-5CrossRefPubMedPubMedCentral

47.

Peschon JJ, Morrissey PJ, Grabstein KH et al (1994) Early lymphocyte expansion is severely impaired in interleukin 7 receptor-deficient mice. J Exp Med 180(5):1955–1960. https://doi.org/10.1084/jem.180.5.1955CrossRefPubMed

48.

Sumaria N, Roediger B, Ng LG et al (2011) Cutaneous immunosurveillance by self-renewing dermal gammadelta T cells. J Exp Med 208(3):505–518. https://doi.org/10.1084/jem.20101824CrossRefPubMedPubMedCentral

49.

Kim MY, Jayasinghe R, Devenport JM et al (2022) A long-acting interleukin-7, rhIL-7-hyFc, enhances CAR T cell expansion, persistence, and anti-tumor activity. Nat Commun 13(1):3296. https://doi.org/10.1038/s41467-022-30860-0CrossRefPubMedPubMedCentral

50.

Hombach AA, Geumann U, Günther C, Hermann FG, Abken H (2020) IL7-IL12 engineered mesenchymal stem cells (MSCs) improve a CAR T cell attack against colorectal cancer cells. Cells. https://doi.org/10.3390/cells9040873CrossRefPubMedPubMedCentral

51.

Swan SL, Mehta N, Ilich E et al (2023) IL7 and IL7 Flt3L co-expressing CAR T cells improve therapeutic efficacy in mouse EGFRvIII heterogeneous glioblastoma. Front Immunol 14:1085547. https://doi.org/10.3389/fimmu.2023.1085547CrossRefPubMedPubMedCentral

52.

Byun HK, Kim K-J, Han SC, Seong J (2021) Effect of interleukin-7 on radiation-induced lymphopenia and its antitumor effects in a mouse model. Int J Radiat Oncol Biol Phys 109(5):1559–1569. https://doi.org/10.1016/j.ijrobp.2020.12.004CrossRefPubMed

53.

Zhao Y, Wei K, Chi H, Xia Z, Li X (2022) IL-7: A promising adjuvant ensuring effective T cell responses and memory in combination with cancer vaccines? Front Immunol 13:1022808. https://doi.org/10.3389/fimmu.2022.1022808CrossRefPubMedPubMedCentral

54.

Terrazzini N, Mantegani P, Kern F, Fortis C, Mondino A, Caserta S (2018) Interleukin-7 unveils pathogen-specific T cells by enhancing antigen-recall responses. J Infect Dis 217(12):1997–2007. https://doi.org/10.1093/infdis/jiy096CrossRefPubMedPubMedCentral

55.

Colpitts SL, Dalton NM, Scott P (2009) IL-7 receptor expression provides the potential for long-term survival of both CD62Lhigh central memory T cells and Th1 effector cells during Leishmania major infection. J Immunol 182(9):5702–5711. https://doi.org/10.4049/jimmunol.0803450CrossRefPubMed

56.

Yi F, Pereira L, Hoffman JA et al (2011) Opposing effects of Tcf3 and Tcf1 control Wnt stimulation of embryonic stem cell self-renewal. Nat Cell Biol 13(7):762–770. https://doi.org/10.1038/ncb2283CrossRefPubMedPubMedCentral

57.

Zhang Y, Wang X (2020) Targeting the Wnt/β-catenin signaling pathway in cancer. J Hematol Oncol 13(1):165. https://doi.org/10.1186/s13045-020-00990-3CrossRefPubMedPubMedCentral

58.

Zhou X, Yu S, Zhao D-M, Harty JT, Badovinac VP, Xue H-H (2010) Differentiation and persistence of memory CD8(+) T cells depend on T cell factor 1. Immunity 33(2):229–240. https://doi.org/10.1016/j.immuni.2010.08.002CrossRefPubMedPubMedCentral

59.

Raghu D, Xue H-H, Mielke LA (2019) Control of lymphocyte Fate, infection, and tumor immunity by TCF-1. Trends Immunol 40(12):1149–1162. https://doi.org/10.1016/j.it.2019.10.006CrossRefPubMed

60.

Zhou X, Xue H-H (2012) Cutting edge: generation of memory precursors and functional memory CD8+ T cells depends on T cell factor-1 and lymphoid enhancer-binding factor-1. J Immunol 189(6):2722–2726. https://doi.org/10.4049/jimmunol.1201150CrossRefPubMed

61.

Utzschneider DT, Charmoy M, Chennupati V et al (2016) T cell factor 1-expressing memory-like CD8(+) T cells sustain the immune response to chronic viral infections. Immunity 45(2):415–427. https://doi.org/10.1016/j.immuni.2016.07.021CrossRefPubMed

62.

Wu T, Ji Y, Moseman EA et al (2016) The TCF1-Bcl6 axis counteracts type I interferon to repress exhaustion and maintain T cell stemness. Sci Immunol. https://doi.org/10.1126/sciimmunol.aai8593CrossRefPubMedPubMedCentral

63.

Im SJ, Hashimoto M, Gerner MY et al (2016) Defining CD8+ T cells that provide the proliferative burst after PD-1 therapy. Nature 537(7620):417–421. https://doi.org/10.1038/nature19330CrossRefPubMedPubMedCentral

64.

Koh J, Kim S, Woo YD et al (2022) TCF1+PD-1+ tumour-infiltrating lymphocytes predict a favorable response and prolonged survival after immune checkpoint inhibitor therapy for non-small-cell lung cancer. Eur J Cancer 174:10–20. https://doi.org/10.1016/j.ejca.2022.07.004CrossRefPubMed

65.

Silva SL, Albuquerque AS, Serra-Caetano A et al (2016) Human naïve regulatory T-cells feature high steady-state turnover and are maintained by IL-7. Oncotarget 7(11):12163–12175. https://doi.org/10.18632/oncotarget.7512CrossRefPubMedPubMedCentral

66.

Mazzucchelli R, Hixon JA, Spolski R et al (2008) Development of regulatory T cells requires IL-7Ralpha stimulation by IL-7 or TSLP. Blood 112(8):3283–3292. https://doi.org/10.1182/blood-2008-02-137414CrossRefPubMedPubMedCentral

67.

Campbell DJ (2015) Control of regulatory T cell migration, function, and homeostasis. J Immunol 195(6):2507–2513. https://doi.org/10.4049/jimmunol.1500801CrossRefPubMed

68.

Tsyklauri O, Chadimova T, Niederlova V et al (2023) Regulatory T cells suppress the formation of potent KLRK1 and IL-7R expressing effector CD8 T cells by limiting IL-2. Elife. https://doi.org/10.7554/eLife.79342CrossRefPubMedPubMedCentral

69.

Widmer MB, Morrissey PJ, Goodwin RG et al (1990) Lymphopoiesis and IL-7. Int J Cell Cloning 8(Suppl 1):168–170. https://doi.org/10.1002/stem.5530080715CrossRefPubMed

70.

Aurrand-Lions M, Mancini SJC (2018) Murine bone marrow niches from hematopoietic stem cells to B cells. Int J Mol Sci. https://doi.org/10.3390/ijms19082353CrossRefPubMedPubMedCentral

71.

Green DE, Rubin CT (2014) Consequences of irradiation on bone and marrow phenotypes, and its relation to disruption of hematopoietic precursors. Bone 63:87–94. https://doi.org/10.1016/j.bone.2014.02.018CrossRefPubMed

72.

Hu S, Cucinotta FA (2011) Characterization of the radiation-damaged precursor cells in bone marrow based on modeling of the peripheral blood granulocytes response. Health Phys 101(1):67–78. https://doi.org/10.1097/HP.0b013e31820dba65CrossRefPubMed

73.

Yu D-Y, Bai Y-L, Feng Y et al (2020) Which bone marrow sparing strategy and radiotherapy technology is most beneficial in bone marrow-sparing intensity modulated radiation therapy for patients with cervical cancer? Front Oncol 10:554241. https://doi.org/10.3389/fonc.2020.554241CrossRefPubMedPubMedCentral

74.

Lehar TJ, Kiely JM, Pease GL, Scanlon PW (1966) Effect of focal irradiation on human bone marrow. Am J Roentgenol Radium Ther Nucl Med 96(1):183–190. https://doi.org/10.2214/ajr.96.1.183CrossRefPubMed

75.

Goswitz FA, Andrews GA, Kniseley RM (1963) Effects of local irradiation (Co60 teletherapy) on the peripheral blood and bone marrow. Blood 21:605–619CrossRefPubMed

76.

Bastianutto C, Mian A, Symes J et al (2007) Local radiotherapy induces homing of hematopoietic stem cells to the irradiated bone marrow. Cancer Res 67(21):10112–10116. https://doi.org/10.1158/0008-5472.CAN-07-2192CrossRefPubMed

77.

Pang N, Shi J, Qin L et al (2021) IL-7 and CCL19-secreting CAR-T cell therapy for tumors with positive glypican-3 or mesothelin. J Hematol Oncol 14(1):118. https://doi.org/10.1186/s13045-021-01128-9CrossRefPubMedPubMedCentral

78.

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.4086CrossRefPubMed

79.

Luo H, Su J, Sun R et al (2020) Coexpression of IL7 and CCL21 increases efficacy of CAR-T Cells in solid tumors without requiring preconditioned lymphodepletion. Clin Cancer Res 26(20):5494–5505. https://doi.org/10.1158/1078-0432.CCR-20-0777CrossRefPubMed

80.

Miglani A, Brar TK, Lal D (2023) Unified airway disease: surgical management. Otolaryngol Clin North Am 56(1):169–179. https://doi.org/10.1016/j.otc.2022.09.013CrossRefPubMed

81.

Duan D, Wang K, Wei C et al (2021) The BCMA-targeted fourth-generation CAR-T cells secreting IL-7 and CCL19 for therapy of refractory/recurrent multiple myeloma. Front Immunol 12:609421. https://doi.org/10.3389/fimmu.2021.609421CrossRefPubMedPubMedCentral

Title: IL7 in combination with radiotherapy stimulates a memory T-cell response to improve outcomes in HNSCC models
Authors: Justin Yu
Jacob Gadwa
Richard B. Ross
Michael Knitz
Laurel B. Darragh
Khalid N. M. Abdelazeem
Jessica Beynor
Brooke Neupert
Alexander Nguyen
Diemmy Nguyen
Nicholas Olimpo
Sophia Corbo
Benjamin Van Court
Angelo D’Alessandro
Anthony Saviola
Sana D. Karam
Publication date: 01-05-2024
Publisher: Springer Berlin Heidelberg
Keywords: Radiotherapy
Radioimmunotherapy
Published in: Cancer Immunology, Immunotherapy / Issue 5/2024
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-024-03664-y

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