Cross talk between cancer cells and the immune system is determinant for cancer progression. Emerging evidence demonstrates that GC characteristics such as metastasis, treatment resistance, and disease recurrence are associated with a tumor subpopulation called gastric cancer stem cells (GCSCs). However, the specific interaction between GCSCs and the immune microenvironment is still under investigation. Although immune evasion has been well described for cancer stem cells (CSCs), recent studies show that GCSCs can also regulate the immune system and even benefit from it. This review will provide an overview of bidirectional interactions between CSCs and immune cells in GC, compiling relevant data about how CSCs can induce leukocyte reprogramming, resulting in pro-tumoral immune cells that orchestrate promotion of metastasis, chemoresistance, tumorigenicity, and even increase in number of cancer cells with stem properties. Some immune cells studied are tumor-associated macrophages (TAMs), neutrophils, Th17 and T regulatory (Treg) cells, mesenchymal stem cells (MSCs), and cancer-associated fibroblasts (CAFs), as well as the signaling pathways involved in these pro-tumoral activities. Conversely, although there are cytotoxic leukocytes that can potentially eliminate GCSCs, we describe mechanisms for immune evasion in GCSCs and their clinical implications. Furthermore, we describe current available immunotherapy targeting GCSC-related markers as possible treatment for GC, discussing how the CSC-modified immune microenvironment can mitigate or inactivate these immunotherapies, limiting their effectiveness. Finally, we summarize key concepts and relevant evidence to understand the cross talk between GCSCs and the immune microenvironment as an important process for effective design of therapies against GCSCs that improve the outcome of patients with GC.

中文翻译：

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胃癌干细胞与免疫微环境的交叉对话：促癌因子

癌细胞和免疫系统之间的串扰是癌症进展的决定因素。新出现的证据表明，胃癌的转移、治疗抵抗和疾病复发等特征与称为胃癌干细胞 (GCSC) 的肿瘤亚群有关。然而，GCSCs 与免疫微环境之间的特定相互作用仍在研究中。尽管癌症干细胞 (CSC) 的免疫逃避已经得到很好的描述，但最近的研究表明，GCSC 还可以调节免疫系统，甚至从中受益。本综述将概述 GC 中 CSCs 和免疫细胞之间的双向相互作用，汇编关于 CSCs 如何诱导白细胞重编程的相关数据，从而导致促肿瘤免疫细胞协调促进转移、化学抗性、致瘤性，甚至增加具有干细胞特性的癌细胞数量。研究的一些免疫细胞是肿瘤相关巨噬细胞 (TAM)、中性粒细胞、Th17 和 T 调节 (Treg) 细胞、间充质干细胞 (MSC) 和癌症相关成纤维细胞 (CAF)，以及参与这些前体的信号通路- 肿瘤活动。相反，虽然有可能消除 GCSC 的细胞毒性白细胞，但我们描述了 GCSC 中免疫逃避的机制及其临床意义。此外，我们描述了当前可用的针对 GCSC 相关标志物的免疫疗法作为 GC 的可能治疗方法，讨论了 CSC 修饰的免疫微环境如何减轻或灭活这些免疫疗法，从而限制其有效性。最后，