Clinical research progress of immunotherapy for nasopharyngeal carcinoma

doi:10.3760/cma.j.cn371439-20230120-00060

Abstract

Abstract:

Immunotherapy mainly uses the effector units of the body's immune system to overcome the immune escape or adaptive immune resistance of tumors， accurately identify and remove tumor cells， and normalize or enhance the function of the immune system， which mainly includes cytokine therapy， immune checkpoint inhibition therapy， adoptive cell immunotherapy， tumor vaccine and antibody targeted therapy. The immune characteristics of nasopharyngeal carcinoma make the patients potentially suitable for immunotherapy or combined therapy with radiotherapy and chemotherapy. In recent years， PD-1 inhibitors alone and in combination with chemotherapy have shown good anti-tumor activity and safety in the treatment of recurrent/metastatic nasopharyngeal carcinoma. The incorporation of immune checkpoint inhibitors into the treatment paradigms of nasopharyngeal carcinoma has become a clinical research hot spot.

Key words: Nasopharyngeal neoplasms, Immunotherapy, Immune checkpoint inhibitors, Immunotherapy， adoptive

Gu Anqin, Long Jinhua, Jin Feng. Clinical research progress of immunotherapy for nasopharyngeal carcinoma[J]. Journal of International Oncology, 2023, 50(5): 299-303.

References 39

[1]	Schreiber RD, Old LJ, Smyth MJ. Cancer immunoediting: integra-ting immunity's roles in cancer suppression and promotion[J]. Science, 2011, 331(6024): 1565-1570. DOI: 10.1126/science.1203486. doi: 10.1126/science.1203486 pmid: 21436444
[2]	Mohme M, Riethdorf S, Pantel K. Circulating and disseminated tumour cells—mechanisms of immune surveillance and escape[J]. Nat Rev Clin Oncol, 2017, 14(3): 155-167. DOI: 10.1038/nrclinonc.2016.144. doi: 10.1038/nrclinonc.2016.144
[3]	Vidal P. Interferon α in cancer immunoediting: from elimination to escape[J]. Scand J Immunol, 2020, 91(5): e12863. DOI: 10.1111/sji.12863. doi: 10.1111/sji.12863
[4]	Lee AW, Ma BB, Ng WT, et al. Management of nasopharyngeal carcinoma: current practice and future perspective[J]. J Clin Oncol, 2015, 33(29): 3356-3364. DOI: 10.1200/JCO.2015.60.9347. doi: 10.1200/JCO.2015.60.9347 pmid: 26351355
[5]	Lin M, Zhang XL, You R, et al. Neoantigen landscape in metastatic nasopharyngeal carcinoma[J]. Theranostics, 2021, 11(13): 6427-6444. DOI: 10.7150/thno.53229. doi: 10.7150/thno.53229 pmid: 33995666
[6]	Chen YP, Chan ATC, Le QT, et al. Nasopharyngeal carcinoma[J]. Lancet, 2019, 394(10192): 64-80. DOI: 10.1016/S0140-6736(19)30956-0. doi: 10.1016/S0140-6736(19)30956-0
[7]	Chow JC, Ngan RK, Cheung KM, et al. Immunotherapeutic approaches in nasopharyngeal carcinoma[J]. Expert Opin Biol Ther, 2019, 19(11): 1165-1172. DOI: 10.1080/14712598.2019.1650910. doi: 10.1080/14712598.2019.1650910 pmid: 31361154
[8]	Cai TT, Ye SB, Liu YN, et al. LMP1-mediated glycolysis induces myeloid-derived suppressor cell expansion in nasopharyngeal carcinoma[J]. PLoS Pathog, 2017, 13(7): e1006503. DOI: 10.1371/journal.ppat.1006503. doi: 10.1371/journal.ppat.1006503
[9]	Lo AK, Dawson CW, Lung HL, et al. The role of EBV-encoded LMP1 in the NPC tumor microenvironment: from function to therapy[J]. Front Oncol, 2021, 11: 640207. DOI: 10.3389/fonc.2021.640207. doi: 10.3389/fonc.2021.640207
[10]	Zhang B, Miao T, Shen X, et al. EB virus-induced ATR activation accelerates nasopharyngeal carcinoma growth via M2-type macrophages polarization[J]. Cell Death Dis, 2020, 11(9): 742. DOI: 10.1038/s41419-020-02925-9. doi: 10.1038/s41419-020-02925-9 pmid: 32917854
[11]	Jin S, Li R, Chen MY, et al. Single-cell transcriptomic analysis defines the interplay between tumor cells, viral infection, and the microenvironment in nasopharyngeal carcinoma[J]. Cell Res, 2020, 30(11): 950-965. DOI: 10.1038/s41422-020-00402-8. doi: 10.1038/s41422-020-00402-8
[12]	Gong L, Kwong DL, Dai W, et al. Comprehensive single-cell sequencing reveals the stromal dynamics and tumor-specific cha-racteristics in the microenvironment of nasopharyngeal carcinoma[J]. Nat Commun, 2021, 12(1): 1540. DOI: 10.1038/s41467-021-21795-z. doi: 10.1038/s41467-021-21795-z
[13]	Chen YP, Yin JH, Li WF, et al. Single-cell transcriptomics reveals regulators underlying immune cell diversity and immune subtypes associated with prognosis in nasopharyngeal carcinoma[J]. Cell Res, 2020, 30(11): 1024-1042. DOI: 10.1038/s41422-020-0374-x. doi: 10.1038/s41422-020-0374-x
[14]	Guo L, Chen Y, Wang J, et al. Down-regulation of UL16-binding protein 3 mediated by interferon-gamma impairs immune killing in nasopharyngeal carcinoma[J]. Am J Transl Res, 2020, 12(10): 6509-6523. pmid: 33194048
[15]	Ahmed MM, Gebriel MG, Morad EA, et al. Expression of immune checkpoint regulators, cytotoxic T-lymphocyte antigen-4, and programmed death-ligand 1 in Epstein-Barr virus-associated nasopharyngeal carcinoma[J]. Appl Immunohistochem Mol Morphol, 2021, 29(6): 401-408. DOI: 10.1097/PAI.0000000000000903. doi: 10.1097/PAI.0000000000000903
[16]	Kim TK, Vandsemb EN, Herbst RS, et al. Adaptive immune resistance at the tumour site: mechanisms and therapeutic opportunities[J]. Nat Rev Drug Discov, 2022, 21(7): 529-540. DOI: 10.1038/s41573-022-00493-5. doi: 10.1038/s41573-022-00493-5 pmid: 35701637
[17]	Daassi D, Mahoney KM, Freeman GJ. The importance of exosomal PDL1 in tumour immune evasion[J]. Nat Rev Immunol, 2020, 20(4): 209-215. DOI: 10.1038/s41577-019-0264-y. doi: 10.1038/s41577-019-0264-y
[18]	Fang W, Yang Y, Ma Y, et al. Camrelizumab (SHR-1210) alone or in combination with gemcitabine plus cisplatin for nasopharyngeal carcinoma: results from two single-arm, phase 1 trials[J]. Lancet Oncol, 2018, 19(10): 1338-1350. DOI: 10.1016/S1470-2045(18)30495-9. doi: S1470-2045(18)30495-9 pmid: 30213452
[19]	Mai HQ, Chen QY, Chen D, et al. Toripalimab or placebo plus chemotherapy as first-line treatment in advanced nasopharyngeal carcinoma: a multicenter randomized phase 3 trial[J]. Nat Med, 2021, 27(9): 1536-1543. DOI: 10.1038/s41591-021-01444-0. doi: 10.1038/s41591-021-01444-0
[20]	Wang FH, Wei XL, Feng J, et al. Efficacy, safety, and correlative biomarkers of toripalimab in previously treated recurrent or metastatic nasopharyngeal carcinoma: a phase Ⅱ clinical trial (POLARIS-02)[J]. J Clin Oncol, 2021, 39(7): 704-712. DOI: 10.1200/JCO.20.02712. doi: 10.1200/JCO.20.02712 pmid: 33492986
[21]	Even C, Wang HM, Li SH, et al. Phase Ⅱ, randomized study of spartalizumab (PDR001), an anti-PD-1 antibody, versus chemotherapy in patients with recurrent/metastatic nasopharyngeal cancer[J]. Clin Cancer Res, 2021, 27(23): 6413-6423. DOI: 10.1158/1078-0432.CCR-21-0822. doi: 10.1158/1078-0432.CCR-21-0822
[22]	Swanson MS, Sinha UK. Rationale for combined blockade of PD-1 and CTLA-4 in advanced head and neck squamous cell cancer—review of current data[J]. Oral Oncol, 2015, 51(1): 12-15. DOI: 10.1016/j.oraloncology.2014.10.010. doi: 10.1016/j.oraloncology.2014.10.010 pmid: 25459157
[23]	Buchbinder EI, Desai A. CTLA-4 and PD-1 pathways: similarities, differences, and implications of their inhibition[J]. Am J Clin Oncol, 2016, 39(1): 98-106. DOI: 10.1097/COC.0000000000000239. doi: 10.1097/COC.0000000000000239
[24]	Grimm EA, Mazumder A, Zhang HZ, et al. Lymphokine-activated killer cell phenomenon. Lysis of natural killer-resistant fresh solid tumor cells by interleukin 2-activated autologous human peripheral blood lymphocytes[J]. J Exp Med, 1982, 155(6): 1823-1841. DOI: 10.1084/jem.155.6.1823. doi: 10.1084/jem.155.6.1823 pmid: 6176669
[25]	Chua D, Huang J, Zheng B, et al. Adoptive transfer of autologous Epstein-Barr virus-specific cytotoxic T cells for nasopharyngeal carcinoma[J]. Int J Cancer, 2001, 94(1): 73-80. DOI: 10.1002/ijc.1430. doi: 10.1002/ijc.1430 pmid: 11668481
[26]	Guo X, Zheng H, Luo W, et al. 5T4-specific chimeric antigen receptor modification promotes the immune efficacy of cytokine-induced killer cells against nasopharyngeal carcinoma stem cell-like cells[J]. Sci Rep, 2017, 7(1): 4859. DOI: 10.1038/s41598-017-04756-9. doi: 10.1038/s41598-017-04756-9 pmid: 28687750
[27]	Lee AZE, Tan LSY, Lim CM. Cellular-based immunotherapy in Epstein-Barr virus induced nasopharyngeal cancer[J]. Oral Oncol, 2018, 84: 61-70. DOI: 10.1016/j.oraloncology.2018.07.011. doi: S1368-8375(18)30267-7 pmid: 30115477
[28]	Smith C, Lee V, Schuessler A, et al. Pre-emptive and therapeutic adoptive immunotherapy for nasopharyngeal carcinoma: phenotype and effector function of T cells impact on clinical response[J]. Oncoimmunology, 2017, 6(2): e1273311. DOI: 10.1080/2162402X.2016.1273311. doi: 10.1080/2162402X.2016.1273311
[29]	Cramer JD, Burtness B, Ferris RL. Immunotherapy for head and neck cancer: recent advances and future directions[J]. Oral Oncol, 2019, 99: 104460. DOI: 10.1016/j.oraloncology.2019.104460. doi: 10.1016/j.oraloncology.2019.104460
[30]	Apetoh L, Ladoire S, Coukos G, et al. Combining immunotherapy and anticancer agents: the right path to achieve cancer cure?[J]. Ann Oncol, 2015, 26(9): 1813-1823. DOI: 10.1093/annonc/mdv209. doi: S0923-7534(19)31756-9 pmid: 25922066
[31]	Bailly C, Thuru X, Quesnel B. Combined cytotoxic chemotherapy and immunotherapy of cancer: modern times[J]. NAR Cancer, 2020, 2(1): zcaa002. DOI: 10.1093/narcan/zcaa002. doi: 10.1093/narcan/zcaa002
[32]	Makowska A, Meier S, Shen L, et al. Anti-PD-1 antibody increases NK cell cytotoxicity towards nasopharyngeal carcinoma cells in the context of chemotherapy-induced upregulation of PD-1 and PD-L1[J]. Cancer Immunol Immunother, 2021, 70(2): 323-336. DOI: 10.1007/s00262-020-02681-x. doi: 10.1007/s00262-020-02681-x
[33]	Wu J, Waxman DJ. Immunogenic chemotherapy: dose and schedule dependence and combination with immunotherapy[J]. Cancer Lett, 2018, 419: 210-221. DOI: 10.1016/j.canlet.2018.01.050. doi: S0304-3835(18)30072-7 pmid: 29414305
[34]	Salewski I, Henne J, Engster L, et al. Combined gemcitabine and immune-checkpoint inhibition conquers anti-PD-L1 resistance in low-immunogenic mismatch repair-deficient tumors[J]. Int J Mol Sci, 2021, 22(11): 5990. DOI: 10.3390/ijms22115990. doi: 10.3390/ijms22115990
[35]	Xue Y, Gao S, Gou J, et al. Platinum-based chemotherapy in combination with PD-1/PD-L1 inhibitors: preclinical and clinical studies and mechanism of action[J]. Expert Opin Drug Deliv, 2021, 18(2): 187-203. DOI: 10.1080/17425247.2021.1825376. doi: 10.1080/17425247.2021.1825376
[36]	Zhu L, Chen L. Progress in research on paclitaxel and tumor immunotherapy[J]. Cell Mol Biol Lett, 2019, 24: 40. DOI: 10.1186/s11658-019-0164-y. doi: 10.1186/s11658-019-0164-y pmid: 31223315
[37]	Yang YP, Qu S, et al. Camrelizumab versus placebo in combination with gemcitabine and cisplatin as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (CAPTAIN-1st): a multicentre, randomised, double-blind, phase 3 trial[J]. Lancet Oncol, 2021, 22(8): 1162-1174. DOI: 10.1016/S1470-2045(21)00302-8. doi: 10.1016/S1470-2045(21)00302-8
[38]	Yang YP, Pan JJ, Wang H, et al. Tislelizumab plus chemotherapy as first-line treatment for recurrent or metastatic nasopharyngeal cancer: a multicenter phase 3 trial (RATIONALE-309)[J]. Cancer Cell, 2023, In press. DOI: 10.1016/j.ccell.2023.04.014. doi: 10.1016/j.ccell.2023.04.014
[39]	Yang YP, Zhao YY, Zhou T, et al. A phase Ⅰb study of SHR-1701, a bifunctional fusion protein targeting PD-L1 and TGF-β, in patients with recurrent or metastatic nasopharyngeal carcinoma (RM-NPC)[J]. J Clin Oncol, 2022, 40(16_suppl): 6024. DOI: 10.1200/JCO.2022.40.16_suppl.6024. doi: 10.1200/JCO.2022.40.16_suppl.6024