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宫颈癌的免疫微环境及 IL-2 在肿瘤促进中的作用。

Immune microenvironment of cervical cancer and the role of IL-2 in tumor promotion.

机构信息

Laboratory of Cellular Oncology, Research Unit Cell Differentiation and Cancer, L-4 P.B. FES Zaragoza, National University of Mexico, Av., Guelatao No. 66 Col. Ejercito de Oriente, Iztapalapa, C.P. 09230 Mexico City, Mexico.

Laboratory of Cellular Oncology, Research Unit Cell Differentiation and Cancer, L-4 P.B. FES Zaragoza, National University of Mexico, Av., Guelatao No. 66 Col. Ejercito de Oriente, Iztapalapa, C.P. 09230 Mexico City, Mexico.

出版信息

Cytokine. 2023 Oct;170:156334. doi: 10.1016/j.cyto.2023.156334. Epub 2023 Aug 18.

Abstract

The tumor microenvironment (TME) is a heterogeneous mixture of resident and tumor cells that maintain close communication through their secretion products. The composition of the TME is dynamic and complex among the different types of cancer, where the immune cells play a relevant role in the elimination of tumor cells, however, under certain circumstances they contribute to tumor development. In cervical cancer (CC) the human papilloma virus (HPV) shapes the microenvironment in order to mediate persistent infections that favors transformation and tumor development. Interleukin-2 (IL-2) is an important TME cytokine that induces CD8+ effector T cells and NKs to eliminate tumor cells, however, IL-2 can also suppress the immune response through Treg cells. Recent studies have shown that CC cells express the IL-2 receptor (IL-2R), that are induced to proliferate at low concentrations of exogenous IL-2 through alterations in the JAK/STAT pathway. This review provides an overview of the main immune cells that make up the TME in CC, as well as the participation of IL-2 in the tumor promotion. Finally, it is proposed that the low density of IL-2 produced by immunocompetent cells is used by tumor cells through its IL-2R as a mechanism to proliferate simultaneously depleting this molecule in order to evade immune response.

摘要

肿瘤微环境(TME)是由常驻细胞和肿瘤细胞组成的异质混合物,通过其分泌产物保持密切的通讯。TME 的组成在不同类型的癌症之间是动态和复杂的,其中免疫细胞在消除肿瘤细胞方面发挥着相关作用,但在某些情况下,它们也有助于肿瘤的发展。在宫颈癌(CC)中,人乳头瘤病毒(HPV)塑造了微环境,以介导持续感染,有利于转化和肿瘤发展。白细胞介素-2(IL-2)是一种重要的 TME 细胞因子,它诱导 CD8+效应 T 细胞和自然杀伤细胞(NK)消除肿瘤细胞,然而,IL-2 也可以通过调节性 T 细胞(Treg)抑制免疫反应。最近的研究表明,CC 细胞表达白细胞介素-2 受体(IL-2R),通过 JAK/STAT 途径的改变,在低浓度的外源性 IL-2 诱导下增殖。本综述概述了构成 CC 中 TME 的主要免疫细胞,以及 IL-2 在肿瘤促进中的参与。最后,提出免疫细胞产生的低浓度 IL-2 被肿瘤细胞通过其 IL-2R 利用作为同时增殖的机制,同时耗尽这种分子以逃避免疫反应。

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