免疫微环境在宫颈癌中的研究进展

doi:10.3760/cma.j.cn371439-20220715-00009

摘要/Abstract

摘要：

淋巴细胞亚群、肿瘤相关巨噬细胞等作为肿瘤微环境中主要的免疫细胞，与其分泌的细胞因子相互作用共同构成免疫微环境，已成为宫颈癌复发转移的重要参与者，亦可影响宫颈癌同步放化疗的敏感性，进而影响患者的疗效和预后。近年来以免疫微环境为基础的宫颈癌免疫和靶向治疗已成为宫颈癌领域的研究热点。

关键词: 宫颈肿瘤, 肿瘤微环境, 化放疗, 免疫疗法

Abstract:

Lymphocyte subsets and tumor-associated macrophages， which are the primary immune cells in the tumor microenvironment， interacts with its released cytokines to form the immunological microenvironment. It has grown to be a significant factor in the recurrence and metastasis of cervical cancer and influences the effectiveness of concurrent radiotherapy and chemotherapy for the disease， which in turn influences the prognosis and outcome of patients. Immunotherapy and targeted therapy for cervical cancer based on the immune microenvironment have grown in popularity as research topics in recent years.

Key words: Uterine cervical neoplasms, Tumor microenvironment, Chemoradiotherapy, Immunotherapy

马雪艳, 鲁历历, 孙鹏飞. 免疫微环境在宫颈癌中的研究进展[J]. 国际肿瘤学杂志, 2023, 50(1): 47-50.

Ma Xueyan, Lu Lili, Sun Pengfei. Advances in the immune microenvironment in cervical cancer[J]. Journal of International Oncology, 2023, 50(1): 47-50.

参考文献 35

[1]	Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2021, 71(3): 209-249. DOI: 10.3322/caac.21660. doi: 10.3322/caac.21660
[2]	Kudela E, Liskova A, Samec M, et al. The interplay between the vaginal microbiome and innate immunity in the focus of predictive, preventive, and personalized medical approach to combat HPV-induced cervical cancer[J]. EPMA J, 2021, 12(2): 199-220. DOI: 10.1007/s13167-021-00244-3. doi: 10.1007/s13167-021-00244-3 pmid: 34194585
[3]	Yuan Y, Cai X, Shen F, et al. HPV post-infection microenvironment and cervical cancer[J]. Cancer Lett, 2021, 497: 243-254. DOI: 10.1016/j.canlet.2020.10.034. doi: 10.1016/j.canlet.2020.10.034 pmid: 33122098
[4]	Chen XJ, Han LF, Wu XG, et al. Clinical significance of CD163⁺ and CD68⁺ tumor-associated macrophages in high-risk HPV-related cervical cancer[J]. J Cancer, 2017, 8(18): 3868-3875. DOI: 10.7150/jca.21444. doi: 10.7150/jca.21444
[5]	Zhang J, Jin S, Li X, et al. Human papillomavirus type 16 disables the increased natural killer cells in early lesions of the cervix[J]. J Immunol Res, 2019, 2019: 9182979. DOI: 10.1155/2019/9182979. doi: 10.1155/2019/9182979
[6]	Maskey N, Thapa N, Maharjan M, et al. Infiltrating CD4 and CD8 lymphocytes in HPV infected uterine cervical milieu[J]. Cancer Manag Res, 2019, 11: 7647-7655. DOI: 10.2147/CMAR.S217264. doi: 10.2147/CMAR.S217264 pmid: 31616181
[7]	Lin D, Kouzy R, Abi Jaoude J, et al. Microbiome factors in HPV-driven carcinogenesis and cancers[J]. PLoS Pathog, 2020, 16(6): e1008524. DOI: 10.1371/journal.ppat.1008524. doi: 10.1371/journal.ppat.1008524
[8]	Wang X, Huang X, Zhang Y. Involvement of human papillomaviruses in cervical cancer[J]. Front Microbiol, 2018, 9: 2896. DOI: 10.3389/fmicb.2018.02896. doi: 10.3389/fmicb.2018.02896 pmid: 30546351
[9]	de Geus V, Ewing-Graham PC, de Koning W, et al. Identifying molecular changes in early cervical cancer samples of patients that developed metastasis[J]. Front Oncol, 2021, 11: 715077. DOI: 10.3389/fonc.2021.715077. doi: 10.3389/fonc.2021.715077
[10]	Ohno A, Iwata T, Katoh Y, et al. Tumor-infiltrating lymphocytes predict survival outcomes in patients with cervical cancer treated with concurrent chemoradiotherapy[J]. Gynecol Oncol, 2020, 159(2): 329-334. DOI: 10.1016/j.ygyno.2020.07.106. doi: 10.1016/j.ygyno.2020.07.106 pmid: 32829964
[11]	Tang A, Dadaglio G, Oberkampf M, et al. B cells promote tumor progression in a mouse model of HPV-mediated cervical cancer[J]. Int J Cancer, 2016, 139(6): 1358-1371. DOI: 10.1002/ijc.30169. doi: 10.1002/ijc.30169 pmid: 27130719
[12]	Kim SS, Shen S, Miyauchi S, et al. B cells improve overall survival in HPV-associated squamous cell carcinomas and are activated by radiation and PD-1 blockade[J]. Clin Cancer Res, 2020, 26(13): 3345-3359. DOI: 10.1158/1078-0432.CCR-19-3211. doi: 10.1158/1078-0432.CCR-19-3211 pmid: 32193227
[13]	Gutiérrez-Hoya A, Soto-Cruz I. NK cell regulation in cervical cancer and strategies for immunotherapy[J]. Cells, 2021, 10(11): 3104. DOI: 10.3390/cells10113104. doi: 10.3390/cells10113104
[14]	Venancio PA, Consolaro MEL, Derchain SF, et al. Indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase expression in HPV infection, SILs, and cervical cancer[J]. Cancer Cytopathol, 2019, 127(9): 586-597. DOI: 10.1002/cncy.22172. doi: 10.1002/cncy.22172 pmid: 31412167
[15]	Xiang X, Wang J, Lu D, et al. Targeting tumor-associated macrophages to synergize tumor immunotherapy[J]. Signal Transduct Target Ther, 2021, 6(1): 75. DOI: 10.1038/s41392-021-00484-9. doi: 10.1038/s41392-021-00484-9
[16]	Murray PJ, Allen JE, Biswas SK, et al. Macrophage activation and polarization: nomenclature and experimental guidelines[J]. Immunity, 2014, 41(1): 14-20. DOI: 10.1016/j.immuni.2014.06.008. doi: 10.1016/j.immuni.2014.06.008 pmid: 25035950
[17]	Guo F, Kong W, Zhao G, et al. The correlation between tumor-associated macrophage infiltration and progression in cervical carcinoma[J]. Biosci Rep, 2021, 41(5): BSR20203145. DOI:10.1042/BSR20203145. doi: 10.1042/BSR20203145
[18]	Wu L, Liu H, Guo H, et al. Circulating and tumor-infiltrating myeloid-derived suppressor cells in cervical carcinoma patients[J]. Oncol Lett, 2018, 15(6): 9507-9515. DOI: 10.3892/ol.2018.8532. doi: 10.3892/ol.2018.8532 pmid: 29844835
[19]	Liang Y, Lü B, Zhao P, et al. Increased circulating GrMyeloid-derived suppressor cells correlated with tumor burden and survival in locally advanced cervical cancer patient[J]. J Cancer, 2019, 10(6): 1341-1348. DOI: 10.7150/jca.29647. doi: 10.7150/jca.29647 pmid: 31031843
[20]	Lu Z, Zhu M, Marley JL, et al. The combined action of monocytic myeloid-derived suppressor cells and mucosal-associated invariant T cells promotes the progression of cervical cancer[J]. Int J Cancer, 2021, 148(6): 1499-1507. DOI: 10.1002/ijc.33411. doi: 10.1002/ijc.33411 pmid: 33245569
[21]	Zhang L, Yu X, Zheng L, et al. Lineage tracking reveals dynamic relationships of T cells in colorectal cancer[J]. Nature, 2018, 564(7735): 268-272. DOI: 10.1038/s41586-018-0694-x. doi: 10.1038/s41586-018-0694-x
[22]	Bonin CM, Padovani CTJ, da Costa IP, et al. Detection of regulatory T cell phenotypic markers and cytokines in patients with human papillomavirus infection[J]. J Med Virol, 2019, 91(2): 317-325. DOI: 10.1002/jmv.25312. doi: 10.1002/jmv.25312 pmid: 30192406
[23]	舒航, 徐中华, 朱皓晨, 等. 宫颈癌放疗敏感性研究进展[J]. 国际肿瘤学杂志, 2020, 47(8): 496-500. DOI: 10.3760/cma.j.cn371439-20191120-00064. doi: 10.3760/cma.j.cn371439-20191120-00064
[24]	Sato H, Okonogi N, Nakano T. Rationale of combination of anti-PD-1/PD-L1 antibody therapy and radiotherapy for cancer treatment[J]. Int J Clin Oncol, 2020, 25(5): 801-809. DOI: 10.1007/s10147-020-01666-1. doi: 10.1007/s10147-020-01666-1 pmid: 32246277
[25]	Mori Y, Sato H, Kumazawa T, et al. Analysis of radiotherapy-induced alteration of CD8⁺ T cells and PD-L1 expression in patients with uterine cervical squamous cell carcinoma[J]. Oncol Lett, 2021, 21(6): 446. DOI: 10.3892/ol.2021.12707. doi: 10.3892/ol.2021.12707
[26]	崔昌裕. 放疗对宫颈癌患者外周血淋巴细胞亚群及炎症因子水平的影响[D]. 延安: 延安大学, 2022. DOI: 10.27438/d.cnki.gyadu.2022.000621. doi: 10.27438/d.cnki.gyadu.2022.000621
[27]	Jarosz-Biej M, Smolarczyk R, Cichoń T, et al. Tumor microenvironment as a "game changer" in cancer radiotherapy[J]. Int J Mol Sci, 2019, 20(13): 3212. DOI: 10.3390/ijms20133212. doi: 10.3390/ijms20133212
[28]	Zhang Y, Yu M, Jing Y, et al. Baseline immunity and impact of chemotherapy on immune microenvironment in cervical cancer[J]. Br J Cancer, 2021, 124(2): 414-424. DOI: 10.1038/s41416-020-01123-w. doi: 10.1038/s41416-020-01123-w
[29]	Herter JM, Kiljan M, Kunze S, et al. Influence of chemoradiation on the immune microenvironment of cervical cancer patients[J]. Strahlenther Onkol, 2022, Inpress. DOI: 10.1007/s00066-022-02007-z. doi: 10.1007/s00066-022-02007-z
[30]	Chen R, Yang W, Li Y, et al. Effect of immunotherapy on the immune microenvironment in advanced recurrent cervical cancer[J]. Int Immunopharmacol, 2022, 106: 108630. DOI: 10.1016/j.intimp.2022.108630. doi: 10.1016/j.intimp.2022.108630
[31]	Jazaeri AA, Zsiros E, Amaria RN, et al. Safety and efficacy of adoptive cell transfer using autologous tumor infiltrating lymphocytes (LN-145) for treatment of recurrent, metastatic, or persistent cervical carcinoma[J]. J Clin Oncol, 2019, 37(15_suppl): 2538. DOI: 10.1200/JCO.2019.37.15_suppl.2538. doi: 10.1200/JCO.2019.37.15_suppl.2538
[32]	Huang H, Nie CP, Liu XF, et al. Phase Ⅰ study of adjuvant immunotherapy with autologous tumor-infiltrating lymphocytes in locally advanced cervical cancer[J]. J Clin Invest, 2022, 132(15): e157726. DOI: 10.1172/JCI157726. doi: 10.1172/JCI157726
[33]	Aspeslagh S, Postel-Vinay S, Rusakiewicz S, et al. Rationale for anti-OX40 cancer immunotherapy[J]. Eur J Cancer, 2016, 52: 50-66. DOI: 10.1016/j.ejca.2015.08.021. doi: 10.1016/j.ejca.2015.08.021 pmid: 26645943
[34]	Panda A, Rosenfeld JA, Singer EA, et al. Genomic and immunologic correlates of LAG-3 expression in cancer[J]. Oncoimmuno-logy, 2020, 9(1): 1756116. DOI: 10.1080/2162402X.2020.1756116. doi: 10.1080/2162402X.2020.1756116
[35]	Solinas C, De Silva P, Bron D, et al. Significance of TIM3 expression in cancer: from biology to the clinic[J]. Semin Oncol, 2019, 46(4-5): 372-379. DOI: 10.1053/j.seminoncol.2019.08.005. doi: S0093-7754(18)30257-4 pmid: 31733828