三级淋巴结构在肿瘤免疫微环境调节和抗肿瘤治疗中的作用

doi:10.3760/cma.j.cn371439-20221121-00033

摘要/Abstract

摘要：

三级淋巴结构（TLS）是肿瘤免疫细胞浸润的重要通道，肿瘤TLS的存在与患者预后相关，也与多种抗肿瘤治疗的疗效相关。探讨TLS的功能、免疫调控机制以及作为肿瘤预后生物标志物对综合抗肿瘤治疗的潜在价值，可为后续相关研究提供新的思路。

Abstract:

Tertiary lymphoid structures （TLSs） is important channel for tumor immune cell infiltration. The existence of tumor TLSs is not only related to the prognosis of patients， but also to the efficacy of a variety of anti-tumor therapies. To explore the function and immunomodulatory mechanism of TLSs and its potential value as a tumor prognostic biomarker in comprehensive anti-tumor therapy will provide new ideas for follow-up research.

Key words: Tertiary lymphoid structures, Tumor microenvironment, Treatment outcome

曹梦清, 徐志勇, 施毓婷, 王凯. 三级淋巴结构在肿瘤免疫微环境调节和抗肿瘤治疗中的作用[J]. 国际肿瘤学杂志, 2023, 50(3): 169-173.

Cao Mengqing, Xu Zhiyong, Shi Yuting, Wang Kai. Role of tertiary lymphoid structures in tumor immune microenvironment regulation and anti-tumor therapy[J]. Journal of International Oncology, 2023, 50(3): 169-173.

参考文献 39

[1]	Pfannstiel C, Strissel PL, Chiappinelli KB, et al. The tumor immune microenvironment drives a prognostic relevance that correlates with bladder cancer subtypes[J]. Cancer Immunol Res, 2019, 7(6): 923-938. DOI: 10.1158/2326-6066.CIR-18-0758. doi: 10.1158/2326-6066.CIR-18-0758 pmid: 30988029
[2]	Vaghjiani RG, Skitzki JJ. Tertiary lymphoid structures as mediators of immunotherapy response[J]. Cancers (Basel), 2022, 14(15): 3748. DOI: 10.3390/cancers14153748. doi: 10.3390/cancers14153748
[3]	Zhang Y, Wang F, Sun HR, et al. Apatinib combined with PD-L1 blockade synergistically enhances antitumor immune responses and promotes HEV formation in gastric cancer[J]. J Cancer Res Clin Oncol, 2021, 147(8): 2209-2222. DOI: 10.1007/s00432-021-03633-3. doi: 10.1007/s00432-021-03633-3 pmid: 33891173
[4]	Cabrita R, Lauss M, Sanna A, et al. Tertiary lymphoid structures improve immunotherapy and survival in melanoma[J]. Nature, 2020, 577(7791): 561-565. DOI: 10.1038/s41586-019-1914-8. doi: 10.1038/s41586-019-1914-8
[5]	Jia W, Zhang T, Yao Q, et al. Tertiary lymphatic structures in primary hepatic carcinoma: controversy cannot overshadow hope[J]. Front Immunol, 2022, 13: 870458. DOI: 10.3389/fimmu.2022.870458. doi: 10.3389/fimmu.2022.870458
[6]	Dieudé M, Kaci I, Hébert MJ. The impact of programmed cell death on the formation of tertiary lymphoid structures[J]. Front Immunol, 2021, 12: 696311. DOI: 10.3389/fimmu.2021.696311. doi: 10.3389/fimmu.2021.696311
[7]	Schumacher TN, Thommen DS. Tertiary lymphoid structures in cancer[J]. Science, 2022, 375(6576): eabf9419. DOI: 10.1126/science.abf9419. doi: 10.1126/science.abf9419
[8]	Koning JJ, Mebius RE. Stromal cells and immune cells involved in formation of lymph nodes and their niches[J]. Curr Opin Immunol, 2020, 64: 20-25. DOI: 10.1016/j.coi.2020.03.003. doi: S0952-7915(20)30026-1 pmid: 32325389
[9]	KleinJan A, van Nimwegen M, Leman K, et al. Involvement of dendritic cells and Th17 cells in induced tertiary lymphoid structures in a chronic beryllium disease mouse model[J]. Mediators Inflamm, 2021, 2021: 8845966. DOI: 10.1155/2021/8845966. doi: 10.1155/2021/8845966
[10]	Coleby R, Lucchesi D, Pontarini E, et al. Stepwise changes in the murine salivary gland immune response during virally-induced ectopic lymphoid structure formation[J]. Clin Exp Rheumatol, 2021, 39 Suppl 133(6):39-48. DOI: 10.55563/clinexprheumatol/gb7pfc. doi: 10.55563/clinexprheumatol/gb7pfc pmid: 34596023
[11]	Hill DG, Ward A, Nicholson LB, et al. Emerging roles for IL-6 family cytokines as positive and negative regulators of ectopic lymphoid structures[J]. Cytokine, 2021, 146: 155650. DOI: 10.1016/j.cyto.2021.155650. doi: 10.1016/j.cyto.2021.155650
[12]	N J, J T, Sl N, et al. Tertiary lymphoid structures and B lymphocytes in cancer prognosis and response to immunotherapies[J]. Oncoimmunology, 2021, 10(1): 1900508. DOI: 10.1080/2162402X.2021.1900508. doi: 10.1080/2162402X.2021.1900508
[13]	Simmons S, Sasaki N, Umemoto E, et al. High-endothelial cell-derived S1P regulates dendritic cell localization and vascular integrity in the lymph node[J]. Elife, 2019, 8: e41239. DOI: 10.7554/eLife.41239. doi: 10.7554/eLife.41239
[14]	Tooley KA, Escobar G, Anderson AC. Spatial determinants of CD8⁺ T cell differentiation in cancer[J]. Trends Cancer, 2022, 8(8): 642-654. DOI: 10.1016/j.trecan.2022.04.003. doi: 10.1016/j.trecan.2022.04.003
[15]	Asrir A, Tardiveau C, Coudert J, et al. Tumor-associated high endothelial venules mediate lymphocyte entry into tumors and predict response to PD-1 plus CTLA-4 combination immunotherapy[J]. Cancer Cell, 2022, 40(3): 318-334. e9. DOI: 10.1016/j.ccell.2022.01.002. doi: 10.1016/j.ccell.2022.01.002 pmid: 35120598
[16]	Dangaj D, Bruand M, Grimm AJ, et al. Cooperation between constitutive and inducible chemokines enables T cell engraftment and immune attack in solid tumors[J]. Cancer Cell, 2019, 35(6): 885-900. e10. DOI: 10.1016/j.ccell.2019.05.004. doi: S1535-6108(19)30242-9 pmid: 31185212
[17]	Woods AN, Wilson AL, Srivinisan N, et al. Differential expression of homing receptor ligands on tumor-associated vasculature that control CD8 effector t-cell entry[J]. Cancer Immunol Res, 2017, 5(12): 1062-1073. DOI: 10.1158/2326-6066.CIR-17-0190. doi: 10.1158/2326-6066.CIR-17-0190 pmid: 29097419
[18]	Patil NS, Nabet BY, Müller S, et al. Intratumoral plasma cells predict outcomes to PD-L1 blockade in non-small cell lung cancer[J]. Cancer Cell, 2022, 40(3): 289-300. e4. DOI: 10.1016/j.ccell.2022.02.002. doi: 10.1016/j.ccell.2022.02.002 pmid: 35216676
[19]	Siddiqui I, Schaeuble K, Chennupati V, et al. Intratumoral Tcf1⁺ PD-1⁺ CD8⁺ T cells with stem-like properties promote tumor control in response to vaccination and checkpoint blockade immunotherapy[J]. Immunity, 2019, 50(1): 195-211. e10. DOI: 10.1016/j.immuni.2018.12.021. doi: S1074-7613(18)30569-7 pmid: 30635237
[20]	Kurtulus S, Madi A, Escobar G, et al. Checkpoint blockade immunotherapy induces dynamic changes in PD-1^- CD8⁺ tumor-infiltrating T cells[J]. Immunity, 2019, 50(1): 181-194. e6. DOI: 10.1016/j.immuni.2018.11.014. doi: S1074-7613(18)30522-3 pmid: 30635236
[21]	Di Pilato M, Kfuri-Rubens R, Pruessmann JN, et al. CXCR6 positions cytotoxic T cells to receive critical survival signals in the tumor microenvironment[J]. Cell, 2021, 184(17): 4512-4530. e22. DOI: 10.1016/j.cell.2021.07.015. doi: 10.1016/j.cell.2021.07.015 pmid: 34343496
[22]	Mustapha R, Ng K, Monypenny J, et al. Insights into unveiling a potential role of tertiary lymphoid structures in metastasis[J]. Front Mol Biosci, 2021, 8: 661516. DOI: 10.3389/fmolb.2021.661516. doi: 10.3389/fmolb.2021.661516
[23]	Kuwabara S, Tsuchikawa T, Nakamura T, et al. Prognostic rele-vance of tertiary lymphoid organs following neoadjuvant chemoradiotherapy in pancreatic ductal adenocarcinoma[J]. Cancer Sci, 2019, 110(6): 1853-1862. DOI: 10.1111/cas.14023. doi: 10.1111/cas.14023
[24]	Boivin G, Kalambaden P, Faget J, et al. Cellular composition and contribution of tertiary lymphoid structures to tumor immune infiltration and modulation by radiation therapy[J]. Front Oncol, 2018, 8: 256. DOI: 10.3389/fonc.2018.00256. doi: 10.3389/fonc.2018.00256 pmid: 30038899
[25]	Lin Q, Tao P, Wang J, et al. Tumor-associated tertiary lymphoid structure predicts postoperative outcomes in patients with primary gastrointestinal stromal tumors[J]. Oncoimmunology, 2020, 9(1): 1747339. DOI: 10.1080/2162402X.2020.1747339. doi: 10.1080/2162402X.2020.1747339
[26]	Inoue H, Horii R, Ito Y, et al. Tumor-infiltrating lymphocytes affect the efficacy of trastuzumab-based treatment in human epidermal growth factor receptor 2-positive breast cancer[J]. Breast Cancer, 2018, 25(3): 268-274. DOI: 10.1007/s12282-017-0822-8. doi: 10.1007/s12282-017-0822-8 pmid: 29185202
[27]	Qi Z, Xu Z, Zhang L, et al. Overcoming resistance to immune checkpoint therapy in PTEN-null prostate cancer by intermittent anti-PI3Kα/β/δ treatment[J]. Nat Commun, 2022, 13(1): 182. DOI: 10.1038/s41467-021-27833-0. doi: 10.1038/s41467-021-27833-0 pmid: 35013322
[28]	van Dijk N, Gil-Jimenez A, Silina K, et al. Preoperative ipilimumab plus nivolumab in locoregionally advanced urothelial cancer: the NABUCCO trial[J]. Nat Med, 2020, 26(12): 1839-1844. DOI: 10.1038/s41591-020-1085-z. doi: 10.1038/s41591-020-1085-z pmid: 33046870
[29]	Vanhersecke L, Brunet M, Guégan JP, et al. Mature tertiary lymphoid structures predict immune checkpoint inhibitor efficacy in solid tumors independently of PD-L1 expression[J]. Nat Cancer, 2021, 2(8): 794-802. DOI: 10.1038/s43018-021-00232-6. doi: 10.1038/s43018-021-00232-6
[30]	Gray KD, McCloskey JE, Vedvyas Y, et al. PD1 blockade enhances ICAM1-directed CAR T therapeutic efficacy in advanced thyroid cancer[J]. Clin Cancer Res, 2020, 26(22): 6003-6016. DOI: 10.1158/1078-0432.CCR-20-1523. doi: 10.1158/1078-0432.CCR-20-1523
[31]	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 pmid: 32082311
[32]	Li H, Wang J, Liu H, et al. Existence of intratumoral tertiary lymphoid structures is associated with immune cells infiltration and predicts better prognosis in early-stage hepatocellular carcinoma[J]. Aging (Albany NY), 2020, 12(4): 3451-3472. DOI: 10.18632/aging.102821. doi: 10.18632/aging.102821
[33]	Ding GY, Ma JQ, Yun JP, et al. Distribution and density of tertiary lymphoid structures predict clinical outcome in intrahepatic cholangiocarcinoma[J]. J Hepatol, 2022, 76(3): 608-618. DOI: 10.1016/j.jhep.2021.10.030. doi: 10.1016/j.jhep.2021.10.030
[34]	Li H, Liu H, Fu H, et al. Peritumoral tertiary lymphoid structures correlate with protective immunity and improved prognosis in patients with hepatocellular carcinoma[J]. Front Immunol, 2021, 12: 648812. DOI: 10.3389/fimmu.2021.648812. doi: 10.3389/fimmu.2021.648812
[35]	Park HS, Kim YM, Kim S, et al. High endothelial venule is a surrogate biomarker for T-cell inflamed tumor microenvironment and prognosis in gastric cancer[J]. J Immunother Cancer, 2021, 9(10): e003353. DOI: 10.1136/jitc-2021-003353. doi: 10.1136/jitc-2021-003353
[36]	Zhan Z, Shi-Jin L, Yi-Ran Z, et al. High endothelial venules proportion in tertiary lymphoid structure is a prognostic marker and correlated with anti-tumor immune microenvironment in colorectal cancer[J]. Ann Med, 2023, 55(1): 114-126. DOI: 10.1080/07853890.2022.2153911. doi: 10.1080/07853890.2022.2153911 pmid: 36503344
[37]	J Gunderson A, Rajamanickam V, Bui C, et al. Germinal center reactions in tertiary lymphoid structures associate with neoantigen burden, humoral immunity and long-term survivorship in pancreatic cancer[J]. Oncoimmunology, 2021, 10(1): 1900635. DOI: 10.1080/2162402X.2021.1900635. doi: 10.1080/2162402X.2021.1900635
[38]	Ruffin AT, Cillo AR, Tabib T, et al. B cell signatures and tertiary lymphoid structures contribute to outcome in head and neck squamous cell carcinoma[J]. Nat Commun, 2021, 12(1): 3349. DOI: 10.1038/s41467-021-23355-x. doi: 10.1038/s41467-021-23355-x pmid: 34099645
[39]	Meylan M, Petitprez F, Lacroix L, et al. Early hepatic lesions display immature tertiary lymphoid structures and show elevated expression of immune inhibitory and immunosuppressive molecules[J]. Clin Cancer Res, 2020, 26(16): 4381-4389. DOI: 10.1158/1078-0432.CCR-19-2929. doi: 10.1158/1078-0432.CCR-19-2929 pmid: 32269054