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Immunogenic cell death in colon cancer prevention and therapy.
Molecular Carcinogenesis ( IF 3.0 ) Pub Date : 2020-03-25 , DOI: 10.1002/mc.23183
Hang Ruan 1, 2 , Brian J Leibowitz 1, 2 , Lin Zhang 2, 3 , Jian Yu 1, 2
Affiliation  

Colorectal cancer (CRC) is a leading cause of cancer‐related death worldwide. The colonic mucosa constitutes a critical barrier and a major site of immune regulation. The immune system plays important roles in cancer development and treatment, and immune activation caused by chronic infection or inflammation is well‐known to increase cancer risk. During tumor development, neoplastic cells continuously interact with and shape the tumor microenvironment (TME), which becomes progressively immunosuppressive. The clinical success of immune checkpoint blockade therapies is limited to a small set of CRCs with high tumor mutational load and tumor‐infiltrating T cells. Induction of immunogenic cell death (ICD), a type of cell death eliciting an immune response, can therefore help break the immunosuppressive TME, engage the innate components, and prime T cell‐mediated adaptive immunity for long‐term tumor control. In this review, we discuss the current understanding of ICD induced by antineoplastic agents, the influence of driver mutations, and recent developments to harness ICD in colon cancer. Mechanism‐guided combinations of ICD‐inducing agents with immunotherapy and actionable biomarkers will likely offer more tailored and durable benefits to patients with colon cancer.

中文翻译:

免疫原性细胞死亡在结肠癌的预防和治疗中。

大肠癌(CRC)是全球癌症相关死亡的主要原因。结肠粘膜构成关键的屏障和免疫调节的主要部位。免疫系统在癌症的发展和治疗中起着重要作用,众所周知,慢性感染或炎症引起的免疫激活会增加癌症的风险。在肿瘤发展过程中,肿瘤细胞不断与肿瘤微环境(TME)相互作用并形成肿瘤微环境(TME),从而逐渐受到免疫抑制。免疫检查点封锁疗法的临床成功仅限于少数具有高肿瘤突变负荷和肿瘤浸润性T细胞的CRC。免疫原性细胞死亡(ICD)的诱导是一种引发免疫反应的细胞死亡,因此可以帮助打破免疫抑制性TME,与先天成分结合,和T细胞介导的适应性免疫,以长期控制肿瘤。在这篇综述中,我们讨论了抗肿瘤药诱导的ICD的当前理解,驱动程序突变的影响以及在结肠癌中利用ICD的最新进展。机制指导的ICD诱导剂与免疫疗法和可作用生物标志物的组合可能会为结肠癌患者提供更多量身定制且持久的收益。
更新日期:2020-03-25
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