小柯机器人

澳大利亚沃尔特和埃利扎·霍尔医学研究所Marie-Liesse Asselin-Labat等研究人员合作发现，由组织驻留的记忆T细胞发起的早期免疫压力塑造非小细胞肺癌的肿瘤演变。相关论文于2023年4月21日在线发表在《癌细胞》杂志上。

研究人员对从未吸烟者（NS）和曾经吸烟者（ES）的健康肺部和肺癌进行了深度分析，发现在ES肺部具有组织驻留记忆T（T_RM）样表型的细胞增强了免疫监视的证据。在临床前模型中，肿瘤发病前出现的肿瘤特异性或旁观者T_RM样细胞促进了免疫细胞的招募，通过MHC I类蛋白表达的丧失和对免疫检查点抑制剂的抵抗，导致肿瘤免疫逃避。在人类中，只有发生在ES患者身上的肿瘤经历了克隆性免疫规避，与烟草相关的突变特征或致癌驱动因素无关。这些数据表明，在肿瘤发展之前，增强的T_RM样活性塑造了肿瘤免疫原性的演变，并能影响免疫疗法的结果。

据介绍，T_RM细胞对局部感染提供免疫防御，并能抑制癌症的发展。然而，目前还不清楚慢性炎症在多大程度上影响T_RM的激活，以及肿瘤发生前存在于组织中的T_RM细胞是否影响人类的癌症演变。

附：英文原文

Title: Early immune pressure initiated by tissue-resident memory T cells sculpts tumor evolution in non-small cell lung cancer

Author: Clare E. Weeden, Velimir Gayevskiy, Claire Marceaux, Daniel Batey, Tania Tan, Kenta Yokote, Nina Tubau Ribera, Allison Clatch, Susan Christo, Charis E. Teh, Andrew J. Mitchell, Marie Trussart, Lucille C. Rankin, Andreas Obers, Jackson A. McDonald, Kate D. Sutherland, Varun J. Sharma, Graham Starkey, Rohit D’Costa, Phillip Antippa, Tracy Leong, Daniel Steinfort, Louis Irving, Charles Swanton, Claire L. Gordon, Laura K. Mackay, Terence P. Speed, Daniel H.D. Gray, Marie-Liesse Asselin-Labat

Issue&Volume: 2023-04-21

Abstract: Tissue-resident memory T (TRM) cells provide immune defense against local infection and can inhibit cancer progression. However, it is unclear to what extent chronic inflammation impacts TRM activation and whether TRM cells existing in tissues before tumor onset influence cancer evolution in humans. We performed deep profiling of healthy lungs and lung cancers in never-smokers (NSs) and ever-smokers (ESs), finding evidence of enhanced immunosurveillance by cells with a TRM-like phenotype in ES lungs. In preclinical models, tumor-specific or bystander TRM-like cells present prior to tumor onset boosted immune cell recruitment, causing tumor immune evasion through loss of MHC class I protein expression and resistance to immune checkpoint inhibitors. In humans, only tumors arising in ES patients underwent clonal immune evasion, unrelated to tobacco-associated mutagenic signatures or oncogenic drivers. These data demonstrate that enhanced TRM-like activity prior to tumor development shapes the evolution of tumor immunogenicity and can impact immunotherapy outcomes.

DOI: 10.1016/j.ccell.2023.03.019

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(23)00092-2

Cancer Cell：《癌细胞》，创刊于2002年。隶属于细胞出版社，最新IF：38.585
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