黑暗骑士：肠炎相关癌发病机制中的中性粒细胞功能重编程
The Dark Knight: Functional Reprogramming of Neutrophils in the Pathogenesis of Colitis-Associated Cancer
DOI 原文链接
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影响因子:8.2
分区:医学1区 Top / 免疫学2区 肿瘤学2区
发表日期:2024 Oct 01
作者:
Sreya Ghosh, Ivan Zanoni
DOI:
10.1158/2326-6066.CIR-23-0642
摘要
中性粒细胞是主要的髓系细胞，在炎症组织中被招募，是结肠炎过程中关键的参与者，也存在于结肠癌的肿瘤微环境中，参与癌症的起始和生长。中性粒细胞本质上用于保护宿主免受微生物入侵，但在癌症发展过程中，它们可能变为促肿瘤的，促使肿瘤的起始、增长甚至转移，从而在宿主中扮演双重角色。在癌症患者中，促肿瘤的中性粒细胞可能具有免疫抑制作用，并作为疾病进展的标志，但其特性尚未完全阐明。本文综述了中性粒细胞在肠道中如何在炎症状态和免疫抑制状态之间波动，以及它们如何促进肿瘤发展。我们描述了中性粒细胞在炎症性肠病中的抗肿瘤和促肿瘤作用，并强调其引发炎症驱动性结直肠癌的能力。我们还介绍了结肠肿瘤微环境中中性粒细胞群体的功能矛盾，潜在地可被利用以制定预防或逆转高危患者炎症相关结肠癌的治疗策略。
Abstract
Neutrophils are the primary myeloid cells that are recruited to inflamed tissues, and they are key players during colitis, being also present within the tumor microenvironment during the initiation and growth of colon cancer. Neutrophils fundamentally serve to protect the host against microorganism invasion, but during cancer development, they can become protumoral and lead to tumor initiation, growth, and eventually, metastasis-hence, playing a dichotomic role for the host. Protumoral neutrophils in cancer patients can be immunosuppressive and serve as markers for disease progression but their characteristics are not fully defined. In this review, we explore the current knowledge on how neutrophils in the gut fluctuate between an inflammatory or immunosuppressive state and how they contribute to tumor development. We describe neutrophils' antitumoral and protumoral effects during inflammatory bowel diseases and highlight their capacity to provoke the advent of inflammation-driven colorectal cancer. We present the functional ambivalence of the neutrophil populations within the colon tumor microenvironment, which can be potentially exploited to establish therapies that will prevent, or even reverse, inflammation-dependent colon cancer incidence in high-risk patients.