小柯机器人

美国纪念斯隆-凯特琳癌症中心Matthew D. Hellmann等研究人员合作揭示非小细胞肺癌免疫疗法获得性耐药性的临床和分子特征。相关论文于2024年1月11日在线发表在《癌细胞》杂志上。

研究人员发现，在1201名接受PD-(L)1阻断疗法治疗的非小细胞肺癌（NSCLC）患者中，获得性耐药性很常见，在超过60%的初始应答者中出现。获得性耐药性表现为炎症和干扰素（IFN）信号的不同表达。复发肿瘤可通过IFNγ反应基因的上调或稳定表达来区分。IFNγ反应基因的上调与假定的耐药途径有关，其特征是持续的IFN信号、免疫功能障碍和抗原递呈基因突变，这些特征可在体外IFNγ治疗后获得性PD-(L)1阻断耐药的多个小鼠模型中重现。

NSCLC对PD-(L)1阻断剂的获得性抗性与持续但改变的IFN反应有关。获得性耐药性的肿瘤微环境持续发炎，而不是被排斥或遗弃，这可能为有效重编程和逆转获得性耐药性的治疗策略提供依据。

研究人员表示，尽管PD-(L)1阻断剂免疫疗法是肺癌的常规疗法，但人们对获得性耐药性知之甚少。

附：英文原文

Title: Clinical and molecular features of acquired resistance to immunotherapy in non-small cell lung cancer

Author: Danish Memon, Adam J. Schoenfeld, Darwin Ye, George Fromm, Hira Rizvi, Xiang Zhang, Mohamed Reda Keddar, Divij Mathew, Kyung Jin Yoo, Jingya Qiu, Jayon Lihm, Jayalaksmi Miriyala, Jennifer L. Sauter, Jia Luo, Andrew Chow, Umesh K. Bhanot, Caroline McCarthy, Chad M. Vanderbilt, Cailian Liu, Mohsen Abu-Akeel, Andrew J. Plodkowski, Nicholas McGranahan, Marta uksza, Benjamin D. Greenbaum, Taha Merghoub, Ikbel Achour, J. Carl Barrett, Ross Stewart, Pedro Beltrao, Taylor H. Schreiber, Andy J. Minn, Martin L. Miller, Matthew D. Hellmann

Issue&Volume: 2024-01-11

Abstract: Although immunotherapy with PD-(L)1 blockade is routine for lung cancer, little is known about acquired resistance. Among 1,201 patients with non-small cell lung cancer (NSCLC) treated with PD-(L)1 blockade, acquired resistance is common, occurring in >60% of initial responders. Acquired resistance shows differential expression of inflammation and interferon (IFN) signaling. Relapsed tumors can be separated by upregulated or stable expression of IFNγ response genes. Upregulation of IFNγ response genes is associated with putative routes of resistance characterized by signatures of persistent IFN signaling, immune dysfunction, and mutations in antigen presentation genes which can be recapitulated in multiple murine models of acquired resistance to PD-(L)1 blockade after in vitro IFNγ treatment. Acquired resistance to PD-(L)1 blockade in NSCLC is associated with an ongoing, but altered IFN response. The persistently inflamed, rather than excluded or deserted, tumor microenvironment of acquired resistance may inform therapeutic strategies to effectively reprogram and reverse acquired resistance.

DOI: 10.1016/j.ccell.2023.12.013

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(23)00441-5

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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