Diaz J L, Wanta S M, Fishbein T M, Kroemer A
Medstar Georgetown Transplant Institute, Medstar Georgetown University Hospital, Washington, DC, USA -
Minerva Chir. 2015 Aug;70(4):217-30. Epub 2015 Apr 28.
Gastrointestinal (GI) cancers are the most commonly occurring cancer worldwide. Colorectal cancer (CRC) is the second and third most commonly diagnosed cancer in women and men, respectively. Despite the advent of screening and the declining incidence of CRC overall, most patients are not diagnosed at an early, localized stage. Due to resistance to chemotherapy, recurrence, and metastatic disease, those diagnosed with advanced disease have only a 12% 5-year survival rate. Given the overwhelming global impact of CRC, the need for advanced therapy is crucial. Targeted immunotherapy in addition to surgical resection, traditional chemotherapy, and radiation therapy is on the rise. For the purpose of this review, we focused on the advances of immunotherapy, particularly in CRC, with mention of research pertaining to particular advances in immunotherapy for other aspects of the GI system. We review basic immunology and the microenvironment surrounding colorectal tumors that lead to immune system evasion and poor responses to chemotherapy. We also examined the way these obstacles are proving to be the targets of tumor specific immunotherapy. We will present current FDA approved immunotherapies such as monoclonal antibodies (mAb) targeting tumor specific antigens, as well as vaccines, adoptive cell therapy, cytokines, and check-point inhibitors. A summation of prior research, current clinical trials, and prospective therapies in murine models help delineate our current status and future strategies on CRC immunotherapy.
胃肠道（GI）癌症是全球最常见的癌症。结直肠癌（CRC）分别是女性和男性中第二和第三大最常被诊断出的癌症。尽管有了筛查手段且CRC的总体发病率在下降，但大多数患者并非在早期局限性阶段被诊断出来。由于对化疗的耐药性、复发和转移性疾病，那些被诊断为晚期疾病的患者5年生存率仅为12%。鉴于CRC对全球的巨大影响，先进疗法的需求至关重要。除了手术切除、传统化疗和放射治疗外，靶向免疫疗法正在兴起。出于本综述的目的，我们重点关注免疫疗法的进展，特别是在CRC方面，同时提及与GI系统其他方面免疫疗法的特定进展相关的研究。我们回顾了基础免疫学以及结直肠肿瘤周围导致免疫系统逃避和对化疗反应不佳的微环境。我们还研究了这些障碍如何被证明是肿瘤特异性免疫疗法的靶点。我们将介绍目前美国食品药品监督管理局（FDA）批准的免疫疗法，如靶向肿瘤特异性抗原的单克隆抗体（mAb），以及疫苗、过继性细胞疗法、细胞因子和检查点抑制剂。对先前研究、当前临床试验以及小鼠模型中的前瞻性疗法的总结有助于勾勒出我们目前在CRC免疫疗法方面的现状和未来策略。
