Yidan Zhang1, Cuthbert Mario Mahenge1, Jordan Krull2, Rand Talal Akasheh1, Laura Chambers3, Xuan Nguyen4, Ting-Yuan David Cheng1
1Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH,2Pelotonia Institute for Immuno-Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH,3Division of Gynecologic Oncology, The Ohio State University Comprehensive Cancer Center – James Cancer Hospital and Solove Research Institute, Columbus, OH,4Department of Radiology, The Ohio State University College of Medicine, Columbus, OH
摘要 Abstract
Background: Variations in the body composition, specifically fat and muscle mass, may influence tissue immune infiltration. However, the relationships between these components and the tumor immune microenvironment in endometrial cancer remain poorly defined. We aimed to investigate whether CT-assessed body composition is associated with tumor immune cell infiltration in endometrial cancer.
Methods: We analyzed 63 patients with endometrial cancer from The Cancer Genome Atlas (TCGA) and the Clinical Proteomic Tumor Analysis Consortium (CPTAC) who had pre-treatment CT body composition measurements at the L3 vertebral level and bulk RNA-seq-based immune deconvolution. Approximately 75% of these patients had endometrioid adenocarcinoma. Immune cell abundances for 22 CIBERSORTx-derived subsets were estimated in absolute mode; subsets with ≥75% zero values were excluded, leaving 14 immune cell types plus the CIBERSORT total immune score for analysis. Eight CT-derived body composition metrics were evaluated, including visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), intermuscular adipose tissue (IMAT), skeletal muscle areas, and corresponding Hounsfield unit (HU)-based density measures. Linear regression models assessed associations between body composition metrics and log1p-transformed immune abundances. Analyses were conducted using univariable and multivariable models adjusting for age and cohort. P-values were corrected for multiple testing using the Benjamini-Hochberg false discovery rate (FDR).
Results: Immune cell abundances were generally low (median<0.10 for most subsets). In univariable models, higher VAT was nominally associated with lower total immune score and reduced abundances of several innate immune subsets, including NK-cell (resting and activated), and macrophage (M0/M1) (all p<0.05). In contrast, several HU-based density metrics, including SATHU and IMATHU, showed nominal positive associations with CD8 T cells. However, no associations remained statistically significant after FDR correction (all FDR ≥0.32). Multivariable models adjusting for age and cohort yielded similar patterns.
Conclusion: In this exploratory cohort, CT-derived body composition metrics showed heterogeneous associations with immune cell infiltration. Visceral adiposity showed potential inverse associations with innate immune infiltration, whereas higher subcutaneous adipose tissue showed potential positive associations with CD8 T-cells. These heterogeneous innate and adaptive immune patterns suggest potential differences in how body composition relates to immune infiltration, warranting further investigation in larger cohorts.
利益披露 Disclosure
Y. Zhang, None..
C. M. Mahenge, None..
J. Krull, None..
R. T. Akasheh, None..
L. Chambers, None..
X. Nguyen, None..
T. D. Cheng, None.