Cancer evolution is a complex process influenced by genetic factors and extracellular stimuli that trigger signaling pathways to coordinate the continuous and dynamic interaction between tumor cells and the elements of the immune system. For over 20 years now, the immune mechanisms controlling cancer progression have been the focus of intensive research. It is well established that the immune system conveys protective antitumor immunity by destroying immunogenic tumor variants, but also facilitates tumor progression by shaping tumor immunogenicity in a process called “immunoediting”. It is also clear that immune-guided tumor editing is associated with tumor evasion from immune surveillance and therefore reinforcing the endogenous antitumor immunity is a desired goal in the context of cancer therapies. The tumor microenvironment (TME) is a complex network which consists of various cell types and factors having important roles regarding tumor development and progression. Tumor infiltrating lymphocytes (TILs) and other tumor infiltrating immune cells (TIICs) are key to our understanding of tumor immune surveillance based on tumor immunogenicity, whereby the densities and location of TILs and TIICs in the tumor regions, as well as their functional programs (comprising the “immunoscore”) have a prominent role for prognosis and prediction for several cancers. The presence of tertiary lymphoid structures (TLS) in the TME or in peritumoral areas has an influence on the locally produced antitumor immune response, and therefore also has a significant prognostic impact. The cross-talk between elements of the immune system with tumor cells in the TME is greatly influenced by hypoxia, the gut and/or the local microbiota, and several metabolic elements, which, in a dynamic interplay, have a crucial role for tumor cell heterogeneity and reprogramming of immune cells along their activation and differentiation pathways. Taking into consideration the recent clinical success with the application immunotherapies for the treatment of several cancer types, increasing endeavors have been made to gain better insights into the mechanisms underlying phenotypic and metabolic profiles in the context of tumor progression and immunotherapy. In this review we will address (i) the role of TILs, TIICs and TLS in breast cancer (BCa); (ii) the different metabolic-based pathways used by immune and breast cancer cells; and (iii) implications for immunotherapy-based strategies in BCa.

癌症进化是一个复杂的过程，受遗传因素和细胞外刺激的影响，这些因素触发信号通路以协调肿瘤细胞与免疫系统成分之间的持续和动态相互作用。20 多年来，控制癌症进展的免疫机制一直是深入研究的焦点。众所周知，免疫系统通过破坏免疫原性肿瘤变体传递保护性抗肿瘤免疫，但也通过在称为“免疫编辑”的过程中塑造肿瘤免疫原性来促进肿瘤进展。同样清楚的是，免疫引导的肿瘤编辑与肿瘤逃避免疫监视有关，因此增强内源性抗肿瘤免疫是癌症治​​疗背景下的理想目标。肿瘤微环境（TME）是一个复杂的网络，由各种细胞类型和对肿瘤发生和进展起重要作用的因子组成。肿瘤浸润淋巴细胞 (TIL) 和其他肿瘤浸润免疫细胞 (TIIC) 是我们了解基于肿瘤免疫原性的肿瘤免疫监视的关键，即肿瘤区域中 TIL 和 TIIC 的密度和位置，以及它们的功能程序。包括“免疫评分”）对几种癌症的预后和预测具有重要作用。TME 或肿瘤周围区域存在三级淋巴结构 (TLS) 会影响局部产生的抗肿瘤免疫反应，因此也具有显着的预后影响。免疫系统元素与 TME 中肿瘤细胞之间的串扰受到缺氧、肠道和/或局部微生物群以及几种代谢元素的极大影响，这些元素在动态相互作用中对肿瘤细胞起着至关重要的作用免疫细胞沿其激活和分化途径的异质性和重编程。考虑到最近在应用免疫疗法治疗几种癌症类型方面取得的临床成功，已做出越来越多的努力以更好地了解肿瘤进展和免疫疗法背景下的表型和代谢特征的机制。在这篇综述中，我们将讨论 (i) TIL、TIIC 和 TLS 在乳腺癌 (BCa) 中的作用；(ii) 免疫和乳腺癌细胞使用的不同代谢途径；