纽约大学医学院George Miller综述了胰腺癌患者抗肿瘤免疫的调控。该综述于2020年8月17日在线发表在国际学术期刊《自然-免疫学》上。

胰腺导管腺癌的预后差而现有治疗方法几乎无法改善预后。在绝大多数胰腺癌患者中基于检查点的免疫疗法并不起作用。与致癌基因KRAS诱导炎症相关的肿瘤细胞内在机制一致，耐受性髓样细胞浸润已成为适应性抗肿瘤免疫反应的关键屏障。

此外，肿瘤内微生物组的发现以及阻碍抗肿瘤免疫宿主-微生物相互作用的阐明也为肿瘤治疗提供了机会。

在本综述中研究人员回顾了胰腺导管腺癌免疫治疗耐药性的机制，并讨论了髓样细胞和微生物组靶向方法相结合直接增强T细胞反应的策略，这些方法可能使免疫疗法有效控制这种恶性肿瘤。

附：英文原文

Title: Regulation and modulation of antitumor immunity in pancreatic cancer

Author: Joshua Leinwand, George Miller

Issue&Volume: 2020-08-17

Abstract: Pancreatic ductal adenocarcinoma carries a dismal prognosis, and outcomes have improved little with modern therapeutics. Checkpoint-based immunotherapy has failed to elicit responses in the vast majority of patients with pancreatic cancer. Alongside tumor cell–intrinsic mechanisms associated with oncogenic KRAS-induced inflammation, the tolerogenic myeloid cell infiltrate has emerged as a critical impediment to adaptive antitumor immune responses. Furthermore, the discovery of an intratumoral microbiome and the elucidation of host–microbe interactions that curtail antitumor immunity also present opportunities for intervention. Here we review the mechanisms of immunotherapy resistance in pancreatic ductal adenocarcinoma and discuss strategies to directly augment T cell responses in parallel with myeloid cell– and microbiome-targeted approaches that may enable immune-mediated control of this malignancy.

DOI: 10.1038/s41590-020-0761-y

Source: https://www.nature.com/articles/s41590-020-0761-y