Paradoxical Effect of Myosteatosis on the Immune Checkpoint Inhibitor Response in Metastatic Renal Cell Carcinoma

作者：Jiwoong Yu, Hyeonju Ahn, Kyung Yeon Han, Wan Song, Hyun Hwan Sung, Hwang Gyun Jeon, Byong Chang Jeong, Seong Il Seo, Seong Soo Jeon, Se Hoon Park, Woong‐Yang Park, Mi Ji Lee, Minyong Kang · 发表于：Journal of Cachexia Sarcopenia and Muscle · 年份：2025 · DOI：10.1002/jcsm.13758 · 被引用次数：8 · 研究领域：Renal cell carcinoma treatment、Cancer Immunotherapy and Biomarkers、Ferroptosis and cancer prognosis

ABSTRACT Background Treatment for metastatic renal cell carcinoma (mRCC) has shifted from tyrosine kinase inhibitor (TKI) therapy to immune checkpoint inhibitor (ICI)–based therapy, improving outcomes but with variable individual responses. This study investigated the prognostic implications of pretreatment low skeletal muscle mass (LSMM) and myosteatosis in patients with mRCC undergoing first‐line ICI‐based therapies, comparing outcomes between PD‐1 inhibitor + CTLA‐4 inhibitor and PD‐1 inhibitor + TKI, incorporating single‐cell RNA sequencing. Methods A retrospective analysis was performed on 90 patients with mRCC treated with ICI‐based therapies between November 2019 and March 2023. Patients were grouped based on whether they received PD‐1 inhibitor + CTLA‐4 inhibitor or PD‐1 inhibitor + TKI combinations. LSMM was defined as skeletal muscle index below 40.8 cm 2 /m 2 for men and 34.9 cm 2 /m 2 for women. Myosteatosis was defined using skeletal muscle density, with cut‐off values < 41 HU for BMI < 25 kg/m 2 and < 33 HU for BMI ≥ 25 kg/m 2 . Progression‐free survival (PFS) and overall survival (OS) were compared using Kaplan–Meier curves and multivariable models. Single‐cell RNA sequencing was performed on pretreatment samples to compare the immune microenvironment between patients with and without myosteatosis. Results The study cohort (26.7% female; median age: 60.5 years) included 59 patients (65.6%) treated with PD‐1 inhibitor + CTLA‐4 inhibitor and 31 patients ...