The Prospect of Harnessing the Microbiome to Improve Immunotherapeutic Response in Pancreatic Cancer.
The Prospect of Harnessing the Microbiome to Improve Immunotherapeutic Response in Pancreatic Cancer.
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DOI：
10.3390/cancers15245708
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发表时间：
2023-12-05
期刊：
影响因子：
5.2
通讯作者：
Thomas, Ryan M.
中科院分区：
文献类型：
--
作者：
Rogers, Sherise;Charles, Angel;Thomas, Ryan M.
胰腺癌是一种隐匿性疾病，通常在其病程后期被诊断出来，此时根治方法尚无定论，5年总体生存率的中位数约为12%。虽然其他恶性肿瘤最近显示出对免疫治疗的反应，但针对胰腺癌的免疫系统在历史上一直没有成功。胰腺癌对免疫治疗的抵抗被认为部分是由于免疫抑制的肿瘤微环境所致。微生物群由生活在病态和与宿主共生关系中的数万亿个微生物组成，最近被证明可以调节几种人类癌症的免疫治疗效果。这篇综述着重于已知的微生物组的相互作用及其在缓解胰腺癌免疫治疗耐药途径方面的潜力，胰腺癌是一种治疗选择有限的致命疾病。预计到2030年，胰腺导管腺癌(PDAC)将成为美国癌症相关死亡的第二大原因。患者通常被诊断为晚期疾病，这解释了令人沮丧的5年中位总存活率约12%。在过去的十年里，免疫疗法成功地改善了包括胃肠癌在内的各种恶性肿瘤的预后。然而，PDAC历史上是一种免疫“冷”瘤，具有免疫抑制环境，免疫细胞进入受限，限制了免疫治疗在这些肿瘤中的成功。微生物群是存在于人类身上和体内的复杂的微生物群落，已被证明与许多癌症有关，包括PDAC。近年来，它在肿瘤免疫学和免疫治疗反应中的作用引起了人们的极大兴趣。在这里，讨论了PDAC中微生物群和免疫治疗相互作用的现状，重点讨论了利用免疫系统对抗胰腺癌所需的研究领域。
Pancreatic cancer is an insidious disease, often diagnosed late in its course when curative treatments are moot, with a 5-year median overall survival of ~12%. While other malignancies have recently shown a response to immunotherapy, targeting the immune system in pancreatic cancer has historically not been successful. Resistance to immunotherapy in pancreatic cancer is believed to be partly due to the immune-suppressive tumor microenvironment. The microbiome, comprised of trillions of microorganisms living in a pathobiont and symbiotic relationship with its host, has recently been demonstrated to modulate the efficacy of immunotherapy in several human cancers. This review focuses on the known interactions of the microbiome and its potential to mitigate pathways for immunotherapy resistance in pancreatic cancer, a deadly disease with limited treatment options. Pancreatic ductal adenocarcinoma cancer (PDAC) is projected to become the second leading cause of cancer-related death in the United States by 2030. Patients are often diagnosed with advanced disease, which explains the dismal 5-year median overall survival rate of ~12%. Immunotherapy has been successful in improving outcomes in the past decade for a variety of malignancies, including gastrointestinal cancers. However, PDAC is historically an immunologically “cold” tumor, one with an immunosuppressive environment and with restricted entry of immune cells that have limited the success of immunotherapy in these tumors. The microbiome, the intricate community of microorganisms present on and within humans, has been shown to contribute to many cancers, including PDAC. Recently, its role in tumor immunology and response to immunotherapy has generated much interest. Herein, the current state of the interaction of the microbiome and immunotherapy in PDAC is discussed with a focus on needed areas of study in order to harness the immune system to combat pancreatic cancer.
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