Bowers Jacob S, Bailey Stefanie R, Rubinstein Mark P, Paulos Chrystal M, Camp E Ramsay
Department of Surgery, Medical University of South Carolina.
Hollings Cancer Center, Medical University of South Carolina.
Oncol Rev. 2019 Aug 1;13(2):430. doi: 10.4081/oncol.2019.430. eCollection 2019 Jul 22.
Pancreatic adenocarcinoma (PDAC) remains a formidable disease that needs improved therapeutic strategies. Even though immunotherapy has revolutionized treatment for various solid tumor types, it remains largely ineffective in treating individuals with PDAC. This review describes how the application of genome-wide analysis is revitalizing the field of PDAC immunotherapy. Major themes include new insights into the body's immune response to the cancer, and key immunosuppressive elements that blunt that antitumor immunity. In particular, new evidence indicates that T cell-based antitumor immunity against PDAC is more common, and more easily generated, than previously thought. However, equally common are an array of cellular and molecular defenses employed by the tumor against those T cells. These discoveries have changed how current immunotherapies are deployed and have directed development of novel strategies to better treat this disease. Thus, the impact of genomic analysis has been two-fold: both in demonstrating the heterogeneity of immune targets and defenses in this disease, as well as providing a powerful tool for designing and identifying personalized therapies that exploit each tumor's unique phenotype. Such personalized treatment combinations may be the key to developing successful immunotherapies for pancreatic adenocarcinoma.
胰腺腺癌(PDAC)仍然是一种难以攻克的疾病,需要改进治疗策略。尽管免疫疗法已经彻底改变了多种实体瘤类型的治疗方式,但在治疗胰腺腺癌患者方面仍然基本无效。这篇综述描述了全基因组分析的应用如何重振胰腺腺癌免疫治疗领域。主要主题包括对机体针对癌症的免疫反应的新见解,以及削弱抗肿瘤免疫力的关键免疫抑制因素。特别是,新证据表明,基于T细胞的针对胰腺腺癌的抗肿瘤免疫力比以前认为的更为常见,也更容易产生。然而,肿瘤针对这些T细胞采用的一系列细胞和分子防御同样常见。这些发现改变了当前免疫疗法的应用方式,并指导了更好治疗这种疾病的新策略的开发。因此,基因组分析的影响是双重的:既证明了这种疾病中免疫靶点和防御的异质性,又为设计和识别利用每个肿瘤独特表型的个性化疗法提供了强大工具。这种个性化治疗组合可能是开发成功的胰腺腺癌免疫疗法的关键。