Kim So-Jung, Ha Ga-Hee, Kim Sun-Hee, Kang Chi-Dug
MD-PhD Program, Pusan National University School of Medicine , Yangsan , South Korea 626-870.
Immunol Invest. 2014;43(6):517-34. doi: 10.3109/08820139.2013.857352. Epub 2013 Dec 2.
Although cancer immunotherapy, which is able to target specifically cancer cells without detrimental effects to normal cell functions, would serve as an ideal therapeutic modality, most of the randomized clinical trials of cancer immunotherapy have not demonstrated a meaningful survival benefit to cancer patients over preexisting therapeutic modalities. Due to the discrepancy between the impressive preclinical results and the limited clinical results, the cancer immunotherapy is not accepted generally as a standard therapy for cancers. A variety of immune escape mechanisms are thought to be involved in this ineffectiveness of cancer immunotherapy. Therefore, elimination of immunosuppressive activities in tumor microenvironment will enhance the effectiveness of cancer immunotherapy, which is currently focused on activation of tumor-specific immune responses. Since there are now increasing evidences showing that many cytotoxic anticancer drugs including targeted agents given in lower-than-therapeutic doses have not only the ability to eliminate tumor cells but can also block the immunosuppressive activities in tumor microenvironments and consequently favor the development of anticancer immune responses, clinically available drugs can be considered for their rapid application to cancer immunotherapies to enhance the efficacy of cancer immunotherapies with marginal effects on cancer treatment.
尽管癌症免疫疗法能够特异性地靶向癌细胞而不对正常细胞功能产生有害影响,堪称一种理想的治疗方式,但大多数癌症免疫疗法的随机临床试验并未显示出相较于现有治疗方式能给癌症患者带来显著的生存获益。由于临床前研究结果令人印象深刻与临床结果有限之间存在差异,癌症免疫疗法尚未被普遍接受为癌症的标准治疗方法。多种免疫逃逸机制被认为与癌症免疫疗法的这种无效性有关。因此,消除肿瘤微环境中的免疫抑制活性将提高癌症免疫疗法的有效性,目前该疗法主要集中于激活肿瘤特异性免疫反应。鉴于现在越来越多的证据表明,许多细胞毒性抗癌药物,包括以低于治疗剂量给药的靶向药物,不仅具有消除肿瘤细胞的能力,还能阻断肿瘤微环境中的免疫抑制活性,从而有利于抗癌免疫反应的发展,因此可以考虑将临床可用药物迅速应用于癌症免疫疗法,以提高对癌症治疗效果甚微的癌症免疫疗法的疗效。