Department of Fundamental Oncology, University of Lausanne, Epalinges, Switzerland.
Ludwig Institute of Cancer Research Lausanne Branch, Epalinges, Switzerland.
Clin Exp Immunol. 2019 Aug;197(2):153-160. doi: 10.1111/cei.13293. Epub 2019 Apr 1.
Cancer immunotherapy unleashing the power of host immunity on eliminating cancer cells represents a critical advance in cancer treatment; however, effective anti-tumor responses are largely dampened by the immunosuppressive tumor microenvironment (TME). Emerging studies have revealed that physiological features in the TME, including glucose deprivation, hypoxia and low pH, established by the metabolically dysregulated cancer cells restrict anti-tumor immunity by impeding the metabolic fitness of tumor-infiltrating cytotoxic CD8 T cells and natural killer (NK) cells. Furthermore, infiltrating immunomodulatory cells with different metabolic preferences also facilitate the establishment of the immunosuppressive TME. Therefore, deciphering the metabolic cross-talk between immune cells and cancer cells in the TME and elucidating the impact of this process during tumorigenesis are needed to harness anti-tumor immunity more effectively. Herein, we summarize the immunosuppressive features of TME and how these features impair anti-tumor immunity. Moreover, we postulate how immune cells may be involved in shaping the metabolic features of cancer cells and discuss how we might improve the anti-tumor functions of tumor-specific T cells by rewiring their metabolic regulations.
癌症免疫疗法利用宿主免疫力消除癌细胞，这是癌症治疗的重大进展；然而，有效的抗肿瘤反应在很大程度上受到免疫抑制性肿瘤微环境（TME）的抑制。新兴的研究表明，肿瘤细胞代谢失调所导致的 TME 中的生理特征，包括葡萄糖剥夺、缺氧和低 pH 值，通过阻碍浸润性细胞毒性 CD8 T 细胞和自然杀伤（NK）细胞的代谢适应性，限制了抗肿瘤免疫。此外，具有不同代谢偏好的浸润性免疫调节细胞也促进了免疫抑制性 TME 的建立。因此，需要破译 TME 中免疫细胞和癌细胞之间的代谢串扰，并阐明这一过程在肿瘤发生过程中的影响，以更有效地利用抗肿瘤免疫。本文总结了 TME 的免疫抑制特征，以及这些特征如何损害抗肿瘤免疫。此外，我们推测免疫细胞如何参与塑造癌细胞的代谢特征，并讨论如何通过重新调整肿瘤特异性 T 细胞的代谢调节来改善其抗肿瘤功能。
