Rutgers Biomedical and Health Sciences, New Jersey Medical School-Cancer Center, Newark, NJ 07103, USA.
Department of Biochemistry and Molecular Biology, Rutgers Biomedical and Health Sciences, New Jersey Medical School-Cancer Center, Newark, NJ 07103, USA.
Cancers (Basel). 2014 Apr 23;6(2):969-97. doi: 10.3390/cancers6020969.
Following the successes of monoclonal antibody immunotherapies (trastuzumab (Herceptin®) and rituximab (Rituxan®)) and the first approved cancer vaccine, Provenge® (sipuleucel-T), investigations into the immune system and how it can be modified by a tumor has become an exciting and promising new field of cancer research. Dozens of clinical trials for new antibodies, cancer and adjuvant vaccines, and autologous T and dendritic cell transfers are ongoing in hopes of identifying ways to re-awaken the immune system and force an anti-tumor response. To date, however, few consistent, reproducible, or clinically-relevant effects have been shown using vaccine or autologous cell transfers due in part to the fact that the immunosuppressive mechanisms of the tumor have not been overcome. Much of the research focus has been on re-activating or priming cytotoxic T cells to recognize tumor, in some cases completely disregarding the potential roles that B cells play in immune surveillance or how a solid tumor should be treated to maximize immunogenicity. Here, we will summarize what is currently known about the induction or evasion of humoral immunity via tumor-induced cytokine/chemokine expression and how formation of tertiary lymphoid structures (TLS) within the tumor microenvironment may be used to enhance immunotherapy response.
继单克隆抗体免疫疗法（曲妥珠单抗（赫赛汀®）和利妥昔单抗（美罗华®））和首个获批的癌症疫苗 Provenge®（sipuleucel-T）取得成功之后，对免疫系统及其如何被肿瘤改变的研究已成为癌症研究中一个令人兴奋且充满希望的新领域。数十项针对新型抗体、癌症和佐剂疫苗以及自体 T 和树突状细胞转移的临床试验正在进行中，以期确定重新激活免疫系统并引发抗肿瘤反应的方法。然而，迄今为止，由于肿瘤的免疫抑制机制尚未克服，疫苗或自体细胞转移的效果很少具有一致性、可重复性或临床相关性。大部分研究重点都放在重新激活或引发细胞毒性 T 细胞识别肿瘤上，在某些情况下完全忽略了 B 细胞在免疫监视中的潜在作用，或者如何处理实体瘤以最大限度地提高免疫原性。在这里，我们将总结目前已知的肿瘤诱导细胞因子/趋化因子表达诱导或逃避体液免疫的情况，以及肿瘤微环境中三级淋巴结构 (TLS) 的形成如何用于增强免疫治疗反应。
