Immunotherapy has shifted the paradigm of cancer treatment. However, the majority of cancer patients display de novo or acquired resistance to immunotherapy. One of the main mechanisms of immunotherapy resistance is the immunosuppressive microenvironment dominated by the myeloid-derived suppressor cells (MDSCs). Emerging evidence demonstrates that genetic or epigenetic aberrations in cancer cells shape the accumulation and activation of MDSCs. Understanding this genotype-immunophenotype relationship is critical to the rational design of combination immunotherapy. Here, we review the mechanisms of how molecular changes in cancer cells induce recruitment and reprogram the function of tumor-infiltrating myeloid cells, particularly MDSCs. Tumor-infiltrating MDSCs elicit various pro-tumor functions to promote tumor cell fitness, immune evasion, angiogenesis, tissue remodeling, and metastasis. Through understanding the genotype-immunophenotype relationship between neoplastic cells and MDSCs, new approaches can be developed to tailor current immunotherapy strategies to improve cancer patient outcomes.

中文翻译：

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癌细胞内在机制通过细胞因子网络调节 MDSC。

免疫疗法改变了癌症治疗的模式。然而，大多数癌症患者对免疫疗法表现出新生或获得性耐药。免疫治疗耐药的主要机制之一是由髓源性抑制细胞 (MDSC) 主导的免疫抑制微环境。新出现的证据表明，癌细胞中的遗传或表观遗传畸变影响了 MDSC 的积累和激活。了解这种基因型-免疫表型关系对于合理设计联合免疫疗法至关重要。在这里，我们回顾了癌细胞分子变化如何诱导肿瘤浸润性骨髓细胞募集和重新编程功能的机制，尤其是 MDSC。肿瘤浸润性 MDSC 引发各种促肿瘤功能，以促进肿瘤细胞适应性、免疫逃避、血管生成、组织重塑和转移。通过了解肿瘤细胞和 MDSC 之间的基因型-免疫表型关系，可以开发新的方法来定制当前的免疫治疗策略，以改善癌症患者的预后。