Presence of Tertiary Lymphoid Structures and Exhausted Tissue-Resident T Cells Determines Clinical Response to PD-1 Blockade in Renal Cell Carcinoma.

IF 29.7 1区医学 Q1 ONCOLOGY

Cancer discovery Pub Date : 2025-05-02 DOI:10.1158/2159-8290.CD-24-0991

Miya B Hugaboom, Lena V Wirth, Kelly Street, Neil Ruthen, Opeyemi A Jegede, Nicholas R Schindler, Valisha Shah, Jacob P Zaemes, Nourhan El Ahmar, Sayed Matar, Varunika Savla, Toni K Choueiri, Thomas Denize, Destiny J West, David F McDermott, Elizabeth R Plimack, Jeffrey A Sosman, Naomi B Haas, Mark N Stein, Robert Alter, Mehmet A Bilen, Michael E Hurwitz, Hans Hammers, Sabina Signoretti, Michael B Atkins, Catherine J Wu, David A Braun

引用次数: 0

Abstract

Significance: We describe a paradigm wherein combined high TLS and low tissue-resident exhausted CD8+ T cells are required for optimal response to PD-1 blockade in RCC. This analysis identifies key determinants of response to PD-1 blockade in advanced RCC and suggests avenues for future immune modulation through rational combination therapy strategies.

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三级淋巴样结构和耗竭的组织驻留T细胞的存在决定了肾细胞癌对PD-1阻断的临床反应。

靶向PD-1通路的免疫检查点抑制剂（ICI）已经改变了晚期肾细胞癌（RCC）的治疗方法，但治疗反应的机制在很大程度上仍然未知。在此，我们对102名参加一线nivolumab (NCT03117309) II期临床试验的患者的RCC生物标本进行转录组学分析，以研究抗pd1单药治疗反应的决定因素。通过大量分析，我们在应答患者中发现了与三级淋巴结构（TLS）相关的基因富集。使用单细胞转录组学和外部队列验证，我们确定了在临床结果较差的患者中富集的组织驻留（ZNF683+ SLAMF7+）耗尽CD8+ T细胞群。综合这些发现，我们发现具有高TLS和低组织驻留耗尽CD8+ T细胞的肿瘤使用纳沃单抗具有优越的临床结果。总之，这些分析有助于加深对肿瘤微环境如何驱动ICI-耐药的理解，并提出合理克服抗pd1单药治疗耐药的可能治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer discovery ONCOLOGY-

CiteScore

22.90

自引率

1.40%

发文量

838

审稿时长

6-12 weeks

期刊介绍： Cancer Discovery publishes high-impact, peer-reviewed articles detailing significant advances in both research and clinical trials. Serving as a premier cancer information resource, the journal also features Review Articles, Perspectives, Commentaries, News stories, and Research Watch summaries to keep readers abreast of the latest findings in the field. Covering a wide range of topics, from laboratory research to clinical trials and epidemiologic studies, Cancer Discovery spans the entire spectrum of cancer research and medicine.