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◆ Cell Reports Medicine2025-10-01· Durvalumab

4-1BB+ Tregs and inhibitory progenitor exhausted T cells confer resistance to anti-PD-L1 and anti-CTLA-4 combination therapy

Junha Cha, Chang Gon Kim, Nam Suk Sim, Gamin Kim, Wonrak Son, Dahee Kim, Yurim Jung, Hyun Jun Hong, Hae Been Lee, Jaehyung Kim, Jinna Kim, Sun Och Yoon, Seokhyeong Go, Jeong‐Ah Kim, Euijung Seong, Seungbyn Baek, Kyung Hwan Kim, Min Hee Hong, Yoon Woo Koh, Insuk Lee, Hye Ryun Kim

原始摘要(英文原文)· Original abstract
regulatory T cells (Tregs) restricting ICI efficacy. These opposing roles of 4-1BB in different cellular contexts may explain the limited benefit of combinatorial immunotherapy observed in clinical trials. We identify two subsets of tumor-reactive progenitor Tex (Tpex): ICI-responsive Tpex1 and ICI-resistant Tpex2, a subset characterized by KLRB1 and IL17R. The balance of Tpex1 and Tpex2 associates with ICI response across multiple cancers, offering insights into sustaining response. This study was registered at ClinicalTrials.gov (NCT03737968).
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4-1BB+ Tregs and inhibitory progenitor exhausted T cells confer resistance to anti-PD-L1 and anti-CTLA-4 combination therapy — 科研速览 Science Skim