Department of Oncology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
Key Laboratory for Molecular Radiation Oncology of Hunan Province, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
J Exp Clin Cancer Res. 2021 Oct 16;40(1):327. doi: 10.1186/s13046-021-02128-w.
The efficacy of cancer immunotherapy largely depends on the tumor microenvironment, especially the tumor immune microenvironment. Emerging studies have claimed that microbes reside within tumor cells and immune cells, suggesting that these microbes can impact the state of the tumor immune microenvironment. For the first time, this review delineates the landscape of intra-tumoral microbes and their products, herein defined as the tumor microbe microenvironment. The role of the tumor microbe microenvironment in the tumor immune microenvironment is multifaceted: either as an immune activator, inhibitor, or bystander. The underlying mechanisms include: (I) the presentation of microbial antigens by cancer cells and immune cells, (II) microbial antigens mimicry shared with tumor antigens, (III) microbe-induced immunogenic cell death, (IV) microbial adjuvanticity mediated by pattern recognition receptors, (V) microbe-derived metabolites, and (VI) microbial stimulation of inhibitory checkpoints. The review further suggests the use of potential modulation strategies of the tumor microbe microenvironment to enhance the efficacy and reduce the adverse effects of checkpoint inhibitors. Lastly, the review highlights some critical questions awaiting to be answered in this field and provides possible solutions. Overall, the tumor microbe microenvironment modulates the tumor immune microenvironment, making it a potential target for improving immunotherapy. It is a novel field facing major challenges and deserves further exploration.
癌症免疫疗法的疗效在很大程度上取决于肿瘤微环境，特别是肿瘤免疫微环境。新出现的研究声称，微生物存在于肿瘤细胞和免疫细胞内，这表明这些微生物可以影响肿瘤免疫微环境的状态。本文首次阐述了肿瘤内微生物及其产物的图谱，将其定义为肿瘤微生物微环境。肿瘤微生物微环境在肿瘤免疫微环境中的作用是多方面的：可以作为免疫激活剂、抑制剂或旁观者。潜在机制包括：(I) 癌细胞和免疫细胞呈递微生物抗原，(II) 微生物抗原与肿瘤抗原的模拟，(III) 微生物诱导的免疫原性细胞死亡，(IV) 模式识别受体介导的微生物佐剂作用，(V) 微生物衍生的代谢物，以及 (VI) 微生物对抑制性检查点的刺激。本文进一步提出了利用肿瘤微生物微环境的潜在调节策略来增强检查点抑制剂的疗效和降低不良反应的建议。最后，本文强调了该领域有待回答的一些关键问题，并提供了可能的解决方案。总的来说，肿瘤微生物微环境调节肿瘤免疫微环境，使其成为改善免疫疗法的潜在靶点。这是一个面临重大挑战的新兴领域，值得进一步探索。
