Salemme Vincenzo, Centonze Giorgia, Cavallo Federica, Defilippi Paola, Conti Laura
Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy.
Front Oncol. 2021 Mar 11;11:610303. doi: 10.3389/fonc.2021.610303. eCollection 2021.
Breast cancer progression is a complex process controlled by genetic and epigenetic factors that coordinate the crosstalk between tumor cells and the components of tumor microenvironment (TME). Among those, the immune cells play a dual role during cancer onset and progression, as they can protect from tumor progression by killing immunogenic neoplastic cells, but in the meanwhile can also shape tumor immunogenicity, contributing to tumor escape. The complex interplay between cancer and the immune TME influences the outcome of immunotherapy and of many other anti-cancer therapies. Herein, we present an updated view of the pro- and anti-tumor activities of the main immune cell populations present in breast TME, such as T and NK cells, myeloid cells, innate lymphoid cells, mast cells and eosinophils, and of the underlying cytokine-, cell-cell contact- and microvesicle-based mechanisms. Moreover, current and novel therapeutic options that can revert the immunosuppressive activity of breast TME will be discussed. To this end, clinical trials assessing the efficacy of CAR-T and CAR-NK cells, cancer vaccination, immunogenic cell death-inducing chemotherapy, DNA methyl transferase and histone deacetylase inhibitors, cytokines or their inhibitors and other immunotherapies in breast cancer patients will be reviewed. The knowledge of the complex interplay that elapses between tumor and immune cells, and of the experimental therapies targeting it, would help to develop new combination treatments able to overcome tumor immune evasion mechanisms and optimize clinical benefit of current immunotherapies.
乳腺癌进展是一个由遗传和表观遗传因素控制的复杂过程，这些因素协调肿瘤细胞与肿瘤微环境（TME）各成分之间的相互作用。其中，免疫细胞在癌症发生和进展过程中发挥着双重作用，因为它们可以通过杀死免疫原性肿瘤细胞来防止肿瘤进展，但同时也可以塑造肿瘤免疫原性，导致肿瘤逃逸。癌症与免疫TME之间复杂的相互作用影响免疫治疗和许多其他抗癌治疗的结果。在此，我们对乳腺TME中主要免疫细胞群体（如T细胞和NK细胞、髓系细胞、固有淋巴细胞、肥大细胞和嗜酸性粒细胞）的促肿瘤和抗肿瘤活性以及潜在的基于细胞因子、细胞间接触和微泡的机制提出了最新观点。此外，还将讨论能够逆转乳腺TME免疫抑制活性的现有和新型治疗选择。为此，将回顾评估CAR-T和CAR-NK细胞、癌症疫苗接种、诱导免疫原性细胞死亡的化疗、DNA甲基转移酶和组蛋白脱乙酰酶抑制剂、细胞因子或其抑制剂以及其他免疫疗法在乳腺癌患者中的疗效的临床试验。了解肿瘤与免疫细胞之间复杂的相互作用以及针对这种相互作用的实验性治疗方法，将有助于开发新的联合治疗方法，以克服肿瘤免疫逃逸机制并优化当前免疫疗法的临床益处。
