调节性T细胞在弥漫大B细胞淋巴瘤肿瘤微环境的作用机制研究进展

何君; 辜学忠; 林雅婷; 李凡

doi:10.12259/j.issn.2095-610X.S20230607

调节性T细胞在弥漫大B细胞淋巴瘤肿瘤微环境的作用机制研究进展

doi: 10.12259/j.issn.2095-610X.S20230607

何君¹,
辜学忠^{1, 2, ,},
林雅婷¹,
李凡¹

1.
云南省第一人民医院血液科/昆明理工大学附属医院血液内科
2.
云南省血液系统疾病临床医学研究中心/云南省血液疾病临床医学中心，云南昆明　650032

基金项目: 国家自然科学基金资助项目（81860030）；云南省基础研究计划-昆明医科大学应用基础研究联合专项基金资助项目[2018FE001（-113） ]；云南省临床医学中心开放项目（2020LCZXKF-XY02）；云南省卫生健康委人才项目（D-2018018）

详细信息

作者简介:
何君（1994～），女，四川遂宁人，在读硕士研究生，主要从事血液系统肿瘤研究及临床工作

通讯作者:
辜学忠，E-mail：gxz76@126.com

中图分类号: R551.2
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出版历程
- 收稿日期: 2023-04-15
- 网络出版日期: 2023-06-16
- 刊出日期: 2023-06-25

Research Progress on the Mechanism of Regulatory T Cells in Tumor Microenvironment of Diffuse Large B-cell Lymphoma

Jun HE¹,
Xuezhong GU^{1, 2
, ,},
Yating LIN¹,
Fan LI¹

1.
Dept. of Hematology，The Affiliated Hospital of Kunming University of Science and Technology/The First People’s Hospital of Yunnan Province
2.
Yunnan Provinccial Clinical Research Center for Hematologic Disease，Yunnan Province Clinical Center for Hematologic Diseases，Kunming Yunnan 650032，China

摘要

摘要: 弥漫大B细胞淋巴瘤是非霍奇金淋巴瘤中最常见的一种，目前CD20单克隆抗体联合化疗使其缓解率较前增加，但仍有部分人群疗效欠佳甚至耐药，仍需要开发新的药物提高缓解率。调节性T细胞作为免疫调节中发挥重要作用的细胞群体，其在弥漫大B细胞淋巴瘤肿瘤微环境中协调细胞和分子网络，介导局部免疫抑制状态，从而促进肿瘤细胞的增殖、迁移。据此有望靶向治疗弥漫大B细胞淋巴瘤。将对调节性T细胞在弥漫大B细胞淋巴瘤肿瘤微环境的作用机制作一综述。
- 弥漫大B细胞淋巴瘤 /
- 调节性T细胞 /
- 肿瘤微环境
Abstract: Diffuse large B-cell lymphoma is the most common type of non-Hodgkin lymphoma. At present, CD20 monoclonal antibody combined with chemotherapy has increased the response rate. However, some people still have poor efficacy or even drug resistance, and new drugs are still needed to improve the response rate. Regulatory T cells play an important role in immune regulation via coordinating cellular and molecular networks in tumor microenvironment in diffuse large B-cell lymphoma, and mediating local immunosuppression, consequently promoting tumor cell proliferation and migration. Therefore, it is promising to target the treatment of diffuse large B-cell lymphoma. This article reviews the mechanisms of regulatory T cells in the diffuse large B-cell lymphoma microenvironment.
- Diffuse large B-cell lymphoma /
- Regulatory T cells /
- Tumor microenvironment

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参考文献(32)

[1]	Liu Y,Zhang L,Wang B,et al. Requirement for POH1 in differentiation and maintenance of regulatory T cells[J]. Cell Death Differ,2019,26(4):751-762. doi: 10.1038/s41418-018-0162-z
[2]	Shin H J,Kim D Y,Chung J,et al. Prognostic impact of peripheral blood T-cell subsets at the time of diagnosis on survival in patients with diffuse large B-cell lymphoma[J]. Acta Haematol,2021,144(4):427-437. doi: 10.1159/000510912
[3]	Peng F,Qin Y,Mu S,et al. Prognostic role of regulatory T cells in lymphoma: A systematic review and meta-analysis[J]. J Cancer Res Clin Oncol,2020,146(12):3123-3135. doi: 10.1007/s00432-020-03398-1
[4]	Carreras J,Lopez-Guillermo A,Kikuti Y Y,et al. High TNFRSF14 and low BTLA are associated with poor prognosis in Follicular Lymphoma and in Diffuse Large B-cell Lymphoma transformation[J]. J Clin Exp Hematop,2019,59(1):1-16. doi: 10.3960/jslrt.19003
[5]	Jiménez-Cortegana C,Palazón-Carrión N,Martin Garcia-Sancho A,et al. Circulating myeloid-derived suppressor cells and regulatory T cells as immunological biomarkers in refractory/relapsed diffuse large B-cell lymphoma: translational results from the R2-GDP-GOTEL trial[J]. J Immunother Cancer,2021,9(6):e002323. doi: 10.1136/jitc-2020-002323
[6]	Xu T,Chai J,Wang K,et al. Tumor immune microenvironment components and checkpoint molecules in anaplastic variant of diffuse large B-cell lymphoma[J]. Front Oncol,2021,11:638154. doi: 10.3389/fonc.2021.638154
[7]	Saleh R,Elkord E. FoxP3⁺ T regulatory cells in cancer: Prognostic biomarkers and therapeutic targets[J]. Cancer Lett,2020,490:174-185. doi: 10.1016/j.canlet.2020.07.022
[8]	Stirm K,Leary P,Bertram K,et al. Tumor cell-derived IL-10 promotes cell-autonomous growth and immune escape in diffuse large B-cell lymphoma[J]. Oncoimmunology,2021,10(1):2003533. doi: 10.1080/2162402X.2021.2003533
[9]	Najafi M,Farhood B,Mortezaee K. Contribution of regulatory T cells to cancer: A review[J]. J Cell Physiol,2019,234(6):7983-7993. doi: 10.1002/jcp.27553
[10]	Lainé A,Labiad O,Hernandez-Vargas H,et al. Regulatory T cells promote cancer immune-escape through integrin αvβ8-mediated TGF-β activation[J]. Nat Commun,2021,12(1):6228. doi: 10.1038/s41467-021-26352-2
[11]	Arima H,Nishikori M,Otsuka Y,et al. B cells with aberrant activation of Notch1 signaling promote Treg and Th2 cell-dominant T-cell responses via IL-33[J]. Blood Adv,2018,2(18):2282-2295. doi: 10.1182/bloodadvances.2018019919
[12]	Whiteside TL. Human regulatory T cells (Treg) and their response to cancer[J]. Expert Rev Precis Med Drug Dev,2019,4(4):215-228. doi: 10.1080/23808993.2019.1634471
[13]	Feng P,Yang Q,Luo L,et al. The kinase PDK1 regulates regulatory T cell survival via controlling redox homeostasis[J]. Theranostics,2021,11(19):9503-9518. doi: 10.7150/thno.63992
[14]	Okuzono Y,Muraki Y,Sato S. TNFR2 pathways are fully active in cancer regulatory T cells[J]. Biosci Biotechnol Biochem,2022,86(3):351-361. doi: 10.1093/bbb/zbab226
[15]	Dehghani M,Shokrgozar N,Ramzi M,et al. The impact of selenium on regulatory T cell frequency and immune checkpoint receptor expression in patients with diffuse large B cell lymphoma (DLBCL)[J]. Cancer Immunol Immunother,2021,70(10):2961-2969. doi: 10.1007/s00262-021-02889-5
[16]	Göschl L,Scheinecker C,Bonelli M. Treg cells in autoimmunity: from identification to Treg-based therapies[J]. Semin Immunopathol,2019,41(3):301-314. doi: 10.1007/s00281-019-00741-8
[17]	Chen Y,Li M,Cao J,et al. CTLA-4 promotes lymphoma progression through tumor stem cell enrichment and immunosuppression[J]. Open Life Sci,2021,16(1):909-919. doi: 10.1515/biol-2021-0094
[18]	Zhong W,Liu X,Zhu Z,et al. High levels of Tim-3⁺Foxp3⁺Treg cells in the tumor microenvironment is a prognostic indicator of poor survival of diffuse large B cell lymphoma patients[J]. Int Immunopharmacol,2021,96:107662. doi: 10.1016/j.intimp.2021.107662
[19]	刘紫嫣,张健,胡雅彬,等. 滤泡调节性T细胞在病毒感染与疫苗免疫中的作用及机制研究进展[J]. 中华实验和临床病毒学杂志,2021,35(1):116-120. doi: 10.3760/cma.j.cn112866-20200924-00254
[20]	Dehghani M,Kalani M,Golmoghaddam H,et al. Aberrant peripheral blood CD4⁺ CD25⁺ FOXP3⁺ regulatory T cells/T helper-17 number is associated with the outcome of patients with lymphoma[J]. Cancer Immunol Immunother,2020,69(9):1917-1928. doi: 10.1007/s00262-020-02591-y
[21]	Lozano T,Conde E,Martín-Otal C,et al. TCR-induced FOXP3 expression by CD8⁺ T cells impairs their anti-tumor activity[J]. Cancer Lett,2022,528:45-58. doi: 10.1016/j.canlet.2021.12.030
[22]	Lužnik Z,Anchouche S,Dana R,et al. Regulatory T cells in angiogenesis[J]. J Immunol,2020,205(10):2557-2565. doi: 10.4049/jimmunol.2000574
[23]	Cioroianu A I,Stinga P I,Sticlaru L,et al. Tumor microenvironment in diffuse large B-cell lymphoma: Role and prognosis[J]. Anal Cell Pathol (Amst),2019,2019:8586354.
[24]	Shen R,Xu P P,Wang N,et al. Influence of oncogenic mutations and tumor microenvironment alterations on extranodal invasion in diffuse large B-cell lymphoma[J]. Clin Transl Med,2020,10(7):e221.
[25]	van Bruggen J A C,Martens A W J,Tonino S H,et al. Overcoming the hurdles of autologous T-cell-based therapies in B-cell non-hodgkin lymphoma[J]. Cancers (Basel),2020,12(12):3837. doi: 10.3390/cancers12123837
[26]	包芳,万文丽,朱明霞,等. 初发弥漫大B细胞淋巴瘤外周血Treg绝对数减少与不良预后的相关性[J]. 中国实验血液学杂志,2021,29(1):91-97. doi: 10.19746/j.cnki.issn1009-2137.2021.01.015
[27]	Chang C,Chen Y P,Medeiros L J,et al. Higher infiltration of intratumoral CD25+ FOXP3+ lymphocytes correlates with a favorable prognosis in patients with diffuse large B-cell lymphoma[J]. Leuk Lymphoma,2021,62(1):76-85. doi: 10.1080/10428194.2020.1817438
[28]	Gao R,Shi G P,Wang J. Functional diversities of regulatory T cells in the context of cancer immunotherapy[J]. Front Immunol,2022,13:833667. doi: 10.3389/fimmu.2022.833667
[29]	Jorapur A,Marshall LA,Jacobson S,et al. EBV+ tumors exploit tumor cell-intrinsic and -extrinsic mechanisms to produce regulatory T cell-recruiting chemokines CCL17 and CCL22[J]. PLoS Pathog,2022,18(1):e1010200. doi: 10.1371/journal.ppat.1010200
[30]	Beheshti S A,Shamsasenjan K,Ahmadi M,et al. CAR Treg: A new approach in the treatment of autoimmune diseases[J]. Int Immunopharmacol,2022,102:108409. doi: 10.1016/j.intimp.2021.108409
[31]	Wagner J C,Tang Q. CAR-tregs as a strategy for inducing graft tolerance[J]. Curr Transplant Rep,2020,7(3):205-214. doi: 10.1007/s40472-020-00285-z
[32]	Rana J,Biswas M. Regulatory T cell therapy:Current and future design perspectivs[J]. Cell Immunol,2020,356:104193. doi: 10.1016/j.cellimm.2020.104193

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