Landreneau Joshua P, Shurin Michael R, Agassandian Marianna V, Keskinov Anton A, Ma Yang, Shurin Galina V
Department of Pathology, Divisions of Experimental Pathology and Clinical Immunopathology, University of Pittsburgh Medical Center, S732 Scaife Hall, 3550 Terrace Street, Pittsburgh, PA, 15261, USA.
Cancer Microenviron. 2015 Aug;8(2):57-64. doi: 10.1007/s12307-013-0141-3. Epub 2013 Nov 29.
Traditionally, anticancer chemotherapy has been generally considered to be strongly immunosuppressive. However, increasing evidence suggests that certain chemotherapeutic agents rely on the induction of antitumor immune responses, in both experimental animal models and patients with cancer. Many of these chemotherapeutic agents exert immunogenic effects via the induction and release of immunostimulatory "danger" signals from dying cancerous cells when used in low doses. New data suggests that several common chemotherapeutic agents may also display direct stimulating effects on immune cells even when applied in ultra-low concentrations (chemoimmunomodulation). Importantly, it is becoming clear that both immune effector cells and immune regulatory cells can be targeted by various chemotherapeutic agents to produce favorable antitumor immune responses. Therefore, utilizing cancer drugs to enhance host antitumor immunity should be considered a feasible therapeutic approach; and recent characterization of the immunomodulatory mechanisms of anticancer chemotherapy using both new and traditional cytotoxic agents suggests that combinations of these approaches with "classical" immunomodulatory agents could lead to a viable new therapeutic paradigm for the treatment of cancer.
传统上，抗癌化疗通常被认为具有很强的免疫抑制作用。然而，越来越多的证据表明，在实验动物模型和癌症患者中，某些化疗药物依赖于诱导抗肿瘤免疫反应。当以低剂量使用时，许多这类化疗药物通过诱导和释放来自垂死癌细胞的免疫刺激“危险”信号发挥免疫原性作用。新数据表明，即使以超低浓度应用，几种常见的化疗药物也可能对免疫细胞表现出直接刺激作用（化学免疫调节）。重要的是，越来越清楚的是，各种化疗药物都可以靶向免疫效应细胞和免疫调节细胞，以产生有利的抗肿瘤免疫反应。因此，利用癌症药物增强宿主抗肿瘤免疫力应被视为一种可行的治疗方法；最近对使用新型和传统细胞毒性药物的抗癌化疗免疫调节机制的表征表明，这些方法与“经典”免疫调节药物的联合应用可能会产生一种可行的癌症治疗新范式。
