Payne Kyle K, Toor Amir A, Wang Xiang-Yang, Manjili Masoud H
Department of Microbiology & Immunology, Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, USA.
Clin Dev Immunol. 2012;2012:760965. doi: 10.1155/2012/760965. Epub 2012 Oct 11.
The advancement of cancer immunotherapy faces barriers which limit its efficacy. These include weak immunogenicity of the tumor, as well as immunosuppressive mechanisms which prevent effective antitumor immune responses. Recent studies suggest that aberrant expression of cancer testis antigens (CTAs) can generate robust antitumor immune responses, which implicates CTAs as potential targets for immunotherapy. However, the heterogeneity of tumor cells in the presence and quantity of CTA expression results in tumor escape from CTA-specific immune responses. Thus, the ability to modulate the tumor cell epigenome to homogenously induce expression of such antigens will likely render the tumor more immunogenic. Additionally, emerging studies suggest that suppression of antitumor immune responses may be overcome by reprogramming innate and adaptive immune cells. Therefore, this paper discusses recent studies which address barriers to successful cancer immunotherapy and proposes a strategy of modulation of tumor-immune cell crosstalk to improve responses in carcinoma patients.
癌症免疫疗法的进展面临着限制其疗效的障碍。这些障碍包括肿瘤的免疫原性较弱，以及阻止有效的抗肿瘤免疫反应的免疫抑制机制。最近的研究表明，癌胚抗原（CTA）的异常表达可产生强大的抗肿瘤免疫反应，这意味着CTA是免疫疗法的潜在靶点。然而，肿瘤细胞在CTA表达的存在和数量上的异质性导致肿瘤逃避CTA特异性免疫反应。因此，调节肿瘤细胞表观基因组以均匀诱导此类抗原表达的能力可能会使肿瘤更具免疫原性。此外，新出现的研究表明，通过对先天性和适应性免疫细胞进行重编程，可以克服抗肿瘤免疫反应的抑制。因此，本文讨论了近期针对成功的癌症免疫疗法障碍的研究，并提出了一种调节肿瘤-免疫细胞相互作用以改善癌症患者反应的策略。
