Full text

Turn on search term navigation

© 2025. This work is published under http://creativecommons.org/licenses/by/4.0/ (the "License"). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

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 cm2/m2 for men and 34.9 cm2/m2 for women. Myosteatosis was defined using skeletal muscle density, with cut‐off values < 41 HU for BMI < 25 kg/m2 and < 33 HU for BMI ≥ 25 kg/m2. 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 (34.4%) treated with PD‐1 inhibitor + TKI. LSMM was present in 18.9% of patients, and myosteatosis in 41.1%, with comparable proportions across groups. During follow‐up, 29 patients (32.2%) died: 16 in the PD‐1 inhibitor + CTLA‐4 inhibitor group and 13 in the PD‐1 inhibitor + TKI group. The overall 1‐year mortality rate was 22.2%, and PFS rate was 53.3%. Myosteatosis predicted poor OS (HR, 5.389; p = 0.008) and PFS (HR, 2.930; p = 0.022) in the PD‐1 inhibitor + TKI group but was protective for PFS (HR, 0.461; p = 0.049) in the PD‐1 inhibitor + CTLA‐4 inhibitor group. LSMM did not significantly affect outcomes in either group. Single‐cell RNA sequencing revealed higher CTLA‐4 expression in regulatory T cells and more effector memory CD8+ T cells in patients with myosteatosis, whereas patients without myosteatosis had more anti‐tumoural non‐classical monocytes.

Conclusions

Myosteatosis negatively impacts OS and PFS in patients with mRCC treated with PD‐1 inhibitor + TKI therapy but is protective for PFS in those treated with PD‐1 inhibitor + CTLA‐4 inhibitor therapy. Altered checkpoint expression and immune cell composition associated with myosteatosis may contribute to these differential responses.

Details

Title
Paradoxical Effect of Myosteatosis on the Immune Checkpoint Inhibitor Response in Metastatic Renal Cell Carcinoma
Author
Yu, Jiwoong 1   VIAFID ORCID Logo  ; Ahn, Hyeonju 1 ; Han, Kyung Yeon 2 ; Song, Wan 1 ; Sung, Hyun Hwan 1 ; Jeon, Hwang Gyun 1 ; Jeong, Byong Chang 1 ; Seo, Seong Il 1 ; Jeon, Seong Soo 1 ; Park, Se Hoon 3 ; Park, Woong‐Yang 2 ; Lee, Ji Hyun 4 ; Kang, Minyong 5   VIAFID ORCID Logo 

 Department of Urology, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul, South Korea 
 Samsung Genome Institute, Samsung Medical Center, Seoul, South Korea 
 Division of Hematology‐Oncology, Department of Internal Medicine, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul, South Korea 
 Department of Radiology, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul, South Korea 
 Department of Urology, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul, South Korea, Samsung Genome Institute, Samsung Medical Center, Seoul, South Korea, Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, South Korea 
Section
ORIGINAL ARTICLE
Publication year
2025
Publication date
Apr 1, 2025
Publisher
John Wiley & Sons, Inc.
ISSN
21905991
e-ISSN
21906009
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
3193880038
Copyright
© 2025. This work is published under http://creativecommons.org/licenses/by/4.0/ (the "License"). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.