Mechanism and application of hypoxia affecting immunotherapy drug resistance

doi:10.3760/cma.j.cn371439-20201105-00093

Abstract

Abstract:

Immunotherapy is a new anti-tumor method. The application of immune checkpoint inhibitor greatly improves the survival benefit for patients, but the drug resistance of immunotherapy affects the efficacy. Therefore, it is very important to explore the mechanism of drug resistance and solve the problem of drug resis-tance in tumor immunotherapy. Hypoxia in tumor microenvironment is the key factor of immune drug resistance. Hypoxia can inhibit the immune cells function and lead to immune escape through various mechanisms. It can be the breakthrough for overcoming the immunotherapy drug resistance that blocking pathway of hypoxia to promote immune resistance. By reviewing the mechanism of immunotherapy drug resistance induced by hypoxia, it is helpful to explore the development prospect of hypoxia-inducible factor-1α (HIF-1α) related targeted drugs in clinical application for immunotherapy.

Key words: Immunotherapy, Drug resistance, neoplasm, Hypoxia-inducible factor 1, alpha subunit, Immune checkpoint inhibitor

Chen Peiyao, Jia Junmei. Mechanism and application of hypoxia affecting immunotherapy drug resistance[J]. Journal of International Oncology, 2021, 48(8): 489-493.

References 39

[1]	Feng RM, Zong YN, Cao SM, et al. Current cancer situation in China: good or bad news from the 2018 Global Cancer Statistics?[J]. Cancer Commun (Lond), 2019,39(1):22. DOI: 10.1186/s40880-019-0368-6. doi: 10.1186/s40880-019-0368-6
[2]	张博, 吴建春, 骆莹滨, 等. 肿瘤免疫治疗及其相关标记物的研究现状与思考[J]. 中国肿瘤临床, 2020,47(11):581-585. DOI: 10.3969/j.issn.1000-8179.2020.11.306. doi: 10.3969/j.issn.1000-8179.2020.11.306
[3]	Haslam A, Gill J, Prasad V. Estimation of the percentage of US patients with cancer who are eligible for immune checkpoint inhibitor drugs[J]. JAMA Netw Open, 2020,3(3):e200423. DOI: 10.1001/jamanetworkopen.2020.0423. doi: 10.1001/jamanetworkopen.2020.0423
[4]	杨蕊菡. 肿瘤免疫治疗的耐药机制[J]. 中国肿瘤生物治疗杂志, 2019,26(5):602-608. DOI: 10.3872/j.issn.1007-385x.2019.05.019. doi: 10.3872/j.issn.1007-385x.2019.05.019
[5]	王相宜, 张锦, 李燕, 等. 肿瘤代谢调控与肿瘤免疫治疗以及代谢分析方法研究进展[J]. 药学学报, 2020,55(9):2080-2091. DOI: 10.16438/j.0513-4870.2020-1025. doi: 10.16438/j.0513-4870.2020-1025
[6]	闫东科, 吕平. 低氧诱导因子及其抑制剂研究进展[J]. 生物技术进展, 2019,9(4):332-340. DOI: 10.19586/j.2095-2341.2019.0027. doi: 10.19586/j.2095-2341.2019.0027
[7]	钱雯川, 王凡. PD-1/PD-L1免疫治疗在恶性肿瘤中的研究进展[J]. 中国肿瘤临床与康复, 2020,27(3):381-382. DOI: 10.13455/j.cnki.cjcor.2020.03.33. doi: 10.13455/j.cnki.cjcor.2020.03.33
[8]	Barsoum IB, Smallwood CA, Siemens DR, et al. A mechanism of hypoxia-mediated escape from adaptive immunity in cancer cells[J]. Cancer Res, 2014,74(3):665-674. DOI: 10.1158/0008-5472.CAN-13-0992. doi: 10.1158/0008-5472.CAN-13-0992 pmid: 24336068
[9]	苏纯洁, 何前进, 毛伟明, 等. 肝癌组织中PD-L1和HIF-1α的相关性研究[J]. 中国现代普通外科进展, 2019,22(1):22-25. DOI: 10.3969/j.issn.1009-9905.2019.01.006. doi: 10.3969/j.issn.1009-9905.2019.01.006
[10]	Hei Y, Teng B, Zeng Z, et al. Multifunctional immunoliposomes combining catalase and PD-L1 antibodies overcome tumor hypoxia and enhance immunotherapeutic effects against melanoma[J]. Int J Nanomedicine, 2020,15:1677-1691. DOI: 10.2147/IJN.S225807. doi: 10.2147/IJN.S225807
[11]	Zuo HX, Jin Y, Wang Z, et al. Curcumol inhibits the expression of programmed cell death-ligand 1 through crosstalk between hypoxia-inducible factor-1α and STAT3 (T705) signaling pathways in hepa-tic cancer[J]. J Ethnopharmacol, 2020,257:112835. DOI: 10.1016/j.jep.2020.112835. doi: 10.1016/j.jep.2020.112835
[12]	Wang Z, Li MY, Zhang ZH, et al. Panaxadiol inhibits programmed cell death-ligand 1 expression and tumour proliferation via hypoxia-inducible factor (HIF)-1α and STAT3 in human colon cancer cells[J]. Pharmacol Res, 2020,155:104727. DOI: 10.1016/j.phrs.2020.104727. doi: S1043-6618(19)32925-1 pmid: 32113874
[13]	鲍轶, 莫娟芬. T细胞耗竭、失能和衰老状态及其与肿瘤免疫治疗的研究进展[J]. 中华医学杂志, 2019,99(7):557-560. DOI: 10.3760/cma.j.issn.0376-2491.2019.07.018. doi: 10.3760/cma.j.issn.0376-2491.2019.07.018
[14]	Cohen AD, Schaer DA, Liu C, et al. Agonist anti-GITR monoclonal antibody induces melanoma tumor immunity in mice by altering regulatory T cell stability and intra-tumor accumulation[J]. PLoS One, 2010,5(5):e10436. DOI: 10.1371/journal.pone.0010436. doi: 10.1371/journal.pone.0010436
[15]	张康. 调节性T细胞在肿瘤免疫治疗中的研究进展[J]. 右江民族医学院学报, 2015,37(4):635-637. DOI: 10.3969/j.issn.1001-5817.2015.04.043. doi: 10.3969/j.issn.1001-5817.2015.04.043
[16]	Wang M, Wang W, Ding J, et al. Downregulation of Rab17 promotes cell proliferation and invasion in non-small cell lung cancer through STAT3/HIF-1α/VEGF signaling[J]. Thorac Cancer, 2020,11(2):379-388. DOI: 10.1111/1759-7714.13278. doi: 10.1111/1759-7714.13278
[17]	Lee YH, Bae HC, Noh KH, et al. Gain of HIF-1α under normoxia in cancer mediates immune adaptation through the AKT/ERK and VEGFA axes[J]. Clin Cancer Res, 2015,21(6):1438-1446. DOI: 10.1158/1078-0432.CCR-14-1979. doi: 10.1158/1078-0432.CCR-14-1979
[18]	安田丽, 李亮亮, 赵丽. 骨髓微环境影响调节性T细胞促进血液恶性肿瘤发展的研究进展[J]. 中国免疫学杂志, 2021, 37(5): 635-640, 封3-封4. DOI: 10.3969/j.issn.1000-484X.2021.05.024. doi: 10.3969/j.issn.1000-484X.2021.05.024
[19]	Liu X, Mo W, Ye J, et al. Regulatory T cells trigger effector T cell DNA damage and senescence caused by metabolic competition[J]. Nat Commun, 2018,9(1):249. DOI: 10.1038/s41467-017-02689-5. doi: 10.1038/s41467-017-02689-5
[20]	Tamura R, Morimoto Y, Sato M, et al. Difference in the hypoxic immunosuppressive microenvironment of patients with neurofibromatosis type 2 schwannomas and sporadic schwannomas[J]. J Neurooncol, 2020,146(2):265-273. DOI: 10.1007/s11060-019-03388-5. doi: 10.1007/s11060-019-03388-5
[21]	Yamazaki H, Tanaka T, Mie K, et al. Assessment of postoperative adjuvant treatment using toceranib phosphate against adenocarcinoma in dogs[J]. J Vet Intern Med, 2020,34(3):1272-1281. DOI: 10.1111/jvim.15768. doi: 10.1111/jvim.15768 pmid: 32267594
[22]	Zhang W, Huang Q, Xiao W, et al. Advances in anti-tumor treatments targeting the CD47/SIRPα axis[J]. Front Immunol, 2020,11:18. DOI: 10.3389/fimmu.2020.00018. doi: 10.3389/fimmu.2020.00018
[23]	Engelbertsen D, Autio A, Verwilligen RAF, et al. Increased lymphocyte activation and atherosclerosis in CD47-deficient mice[J]. Sci Rep, 2019,9(1):10608. DOI: 10.1038/s41598-019-46942-x. doi: 10.1038/s41598-019-46942-x pmid: 31337788
[24]	朱孔黎, 王艳萍, 宋海燕. CD47分子在抗肿瘤免疫中的应用[J]. 中国新药与临床杂志, 2020,39(6):335-341. DOI: 10.14109/j.cnki.xyylc.2020.06.03. doi: 10.14109/j.cnki.xyylc.2020.06.03
[25]	Nigro A, Ricciardi L, Salvato I, et al. Enhanced expression of CD47 is associated with off-target resistance to tyrosine kinase inhibitor gefitinib in NSCLC[J]. Front Immunol, 2020,10:3135. DOI: 10.3389/fimmu.2019.03135. doi: 10.3389/fimmu.2019.03135
[26]	王志宏, 罗龙龙, 彭晖. 靶向CD47抗体药物的研究进展[J]. 国际药学研究杂志, 2019,46(8):565-570. DOI: 10.13220/j.cnki.jipr.2019.08.001. doi: 10.13220/j.cnki.jipr.2019.08.001
[27]	Zhang H, Lu H, Xiang L, et al. HIF-1 regulates CD47 expression in breast cancer cells to promote evasion of phagocytosis and maintenance of cancer stem cells[J]. Proc Natl Acad Sci U S A, 2015,112(45):E6215-E6223. DOI: 10.1073/pnas.1520032112. doi: 10.1073/pnas.1520032112
[28]	Samanta D, Park Y, Ni X, et al. Chemotherapy induces enrichment of CD47⁺/CD73⁺/PDL1⁺ immune evasive triple-negative breast cancer cells[J]. Proc Natl Acad Sci U S A, 2018,115(6):E1239-E1248. DOI: 10.1073/pnas.1718197115. doi: 10.1073/pnas.1718197115
[29]	ElTanbouly MA, Schaafsma E, Noelle RJ, et al. VISTA: coming of age as a multi-lineage immune checkpoint[J]. Clin Exp Immunol, 2020,200(2):120-130. DOI: 10.1111/cei.13415. doi: 10.1111/cei.13415 pmid: 31930484
[30]	Johnston RJ, Su LJ, Pinckney J, et al. VISTA is an acidic pH-selective ligand for PSGL-1[J]. Nature, 2019,574(7779):565-570. DOI: 10.1038/s41586-019-1674-5. doi: 10.1038/s41586-019-1674-5
[31]	Blando J, Sharma A, Higa MG, et al. Comparison of immune infiltrates in melanoma and pancreatic cancer highlights VISTA as a potential target in pancreatic cancer[J]. Proc Natl Acad Sci U S A, 2019,116(5):1692-1697. DOI: 10.1073/pnas.1811067116. doi: 10.1073/pnas.1811067116 pmid: 30635425
[32]	Liu J, Yuan Y, Chen W, et al. Immune-checkpoint proteins VISTA and PD-1 nonredundantly regulate murine T-cell responses[J]. Proc Natl Acad Sci U S A, 2015,112(21):6682-6687. DOI: 10.1073/pnas.1420370112. doi: 10.1073/pnas.1420370112
[33]	Deng J, Li J, Sarde A, et al. Hypoxia-induced VISTA promotes the suppressive function of myeloid-derived suppressor cells in the tumor microenvironment[J]. Cancer Immunol Res, 2019,7(7):1079-1090. DOI: 10.1158/2326-6066.CIR-18-0507. doi: 10.1158/2326-6066.CIR-18-0507 pmid: 31088847
[34]	赵桂增, 张晨光. 人类白细胞抗原G参与免疫调节研究进展[J]. 中国免疫学杂志, 2020,36(15):1913-1916. DOI: 10.3969/j.issn.1000-484X.2020.15.025. doi: 10.3969/j.issn.1000-484X.2020.15.025
[35]	Garziera M, Scarabel L, Toffoli G. Hypoxic modulation of HLA-G expression through the metabolic sensor HIF-1 in human cancer cells[J]. J Immunol Res, 2017,2017:4587520. DOI: 10.1155/2017/4587520. doi: 10.1155/2017/4587520 pmid: 28781970
[36]	Ziliotto M, Rodrigues RM, Chies JAB. Controlled hypobaric hypoxia increases immunological tolerance by modifying HLA-G expression, a potential therapy to inflammatory diseases[J]. Med Hypotheses, 2020,140:109664. DOI: 10.1016/j.mehy.2020.109664. doi: S0306-9877(20)30052-9 pmid: 32155542
[37]	Chen J, Cui B, Fan Y, et al. Protein kinase D1 regulates hypoxic metabolism through HIF-1α and glycolytic enzymes incancer cells[J]. Oncol Rep, 2018,40(2):1073-1082. DOI: 10.3892/or.2018.6479. doi: 10.3892/or.2018.6479
[38]	Halpin-Veszeleiova K, Hatfield SM. Oxygenation and A2AR bloc-kade to eliminate hypoxia/HIF-1α-adenosinergic immunosuppressive axis and improve cancer immunotherapy[J]. Curr Opin Pharmacol, 2020,53:84-90. DOI: 10.1016/j.coph.2020.07.005. doi: S1471-4892(20)30043-6 pmid: 32841869
[39]	Hatfield S, Veszeleiova K, Steingold J, et al. Mechanistic justifications of systemic therapeutic oxygenation of tumors to weaken the hypoxia inducible factor 1α-mediated Immunosuppression[J]. Adv Exp Med Biol, 2019,1136:113-121. DOI: 10.1007/978-3-030-12734-3_8. doi: 10.1007/978-3-030-12734-3_8 pmid: 31201720