小柯机器人

意大利人文大学生物医学科学系Maria Rescigno发现通过微生物群介导的HLA I类上调使癌细胞对免疫检查点抑制剂(ICIs)敏感。该研究于2023年9月21日发表于国际一流学术期刊《癌细胞》杂志上。

他们发现细菌释放的代谢物，特别是植物鞘氨醇，可以上调癌细胞上HLA I类的表达，使它们在体外和体内对肿瘤抗原(TA)特异性细胞毒性T淋巴细胞(CTL)裂解敏感，并结合免疫治疗。这种作用是通过生物后诱导NLRC5响应上游MYD88-NF-κB激活而上调介导的，从而显著控制肿瘤生长。

据悉，最近的数据表明，肠道微生物群对实体瘤患者对ICI的临床反应有重要影响。基于ICI的治疗通过解锁同源CTL效应反应起作用，并且对ICI的敏感性增加是由于患者TA特异性CTL反应的增强。TA特异性CTL清除肿瘤需要相关TAs在癌细胞HLA I类分子上表达，HLA I类表达降低是癌细胞逃避免疫系统的一种常见机制。

附：英文原文

Title: Sensitizing cancer cells to immune checkpoint inhibitors by microbiota-mediated upregulation of HLA class I

Author: Valentina Ferrari, Antonino Lo Cascio, Alessia Melacarne, Nina Tanaskovi, Alessandro M. Mozzarelli, Luca Tiraboschi, Michela Lizier, Marta Salvi, Daniele Braga, Francesca Algieri, Giuseppe Penna, Maria Rescigno

Issue&Volume: 2023-09-21

Abstract: Recent data have shown that gut microbiota has a major impact on the clinical responseto immune checkpoint inhibitors (ICIs) in the context of solid tumors. ICI-based therapyacts by unlocking cognate cytotoxic T lymphocyte (CTL) effector responses, and increasedsensitivity to ICIs is due to an enhancement of patients’ tumor antigen (TA)-specificCTL responses. Cancer clearance by TA-specific CTL requires expression of relevantTAs on cancer cells’ HLA class I molecules, and reduced HLA class I expression isa common mechanism used by cancer cells to evade the immune system. Here, we showthat metabolites released by bacteria, in particular, phytosphingosine, can upregulateHLA class I expression on cancer cells, sensitizing them to TA-specific CTL lysisin vitro and in vivo, in combination with immunotherapy. This effect is mediated by postbiotic-inducedupregulation of NLRC5 in response to upstream MYD88-NF-κB activation, thus significantlycontrolling tumor growth.

DOI: 10.1016/j.ccell.2023.08.014

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(23)00315-X

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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