Deeley Research Centre, BC Cancer Agency, Victoria, BC, Canada.
Immunol Rev. 2012 Sep;249(1):176-94. doi: 10.1111/j.1600-065X.2012.01141.x.
Tumors and the immune system are intertwined in a competition where tilting the fine balance between tumor-specific immunity and tolerance can ultimately decide the fate of the host. Defensive and suppressive immunological responses to cancer are exquisitely sensitive to metabolic features of rapidly growing tumors, such as hypoxia, low nutrient availability, and aberrant growth factor signaling. As a result, clinical therapies impacting these properties change the in situ antitumor immune response by virtue of disrupting the tumor environment. To compensate for disruptions in cellular metabolism, cells activate autophagy to promote survival. On the basis of this notion, strategies designed to block autophagy in tumor cells are currently being tested in several human clinical trials. However, therapies that impair tumor metabolism must also take into account their effect on lymphocytes activated in the immune response to cancer. Given that a strong antitumor immune response is a positive prognostic factor in overall patient survival, identifying ways to block essential processes in tumor cells and suppressive immune cells while promoting those that are important for a robust immune response are of critical importance. Herein, we review the effects of anti-cancer agents that impact metabolism administered concurrently with autophagy inhibitors on immune cells and consider the implications for patient response to therapy.
肿瘤与免疫系统相互交织，形成一场竞争，其中肿瘤特异性免疫与耐受之间的微妙平衡最终决定了宿主的命运。针对癌症的防御性和抑制性免疫反应对快速生长肿瘤的代谢特征非常敏感，如缺氧、营养供应不足和异常生长因子信号。因此，影响这些特性的临床疗法通过破坏肿瘤环境来改变原位抗肿瘤免疫反应。为了弥补细胞代谢的紊乱，细胞会激活自噬以促进存活。基于这一概念，目前正在几项人类临床试验中测试旨在阻断肿瘤细胞自噬的策略。然而，损害肿瘤代谢的疗法还必须考虑其对在癌症免疫反应中被激活的淋巴细胞的影响。鉴于强烈的抗肿瘤免疫反应是患者总生存的一个积极预后因素，因此确定阻断肿瘤细胞和抑制性免疫细胞中必需过程的方法，同时促进对强大免疫反应很重要的过程至关重要。在此，我们综述了同时使用自噬抑制剂和影响代谢的抗癌药物对免疫细胞的影响，并考虑了其对患者对治疗反应的影响。
