Abstract C156: Examining the role of T cell responses in colorectal cancer sex disparities

Abstract Purpose: Persistent sex disparities in colorectal cancer (CRC) incidence and mortality exist and vary by race and ethnicity. The overarching goal of this proposal is to quantify differences in the CRC tumor immune microenvironment by sex in the Latino Colorectal Cancer Consortium (LC3). Methods: The LC3 is a consortium of pooled individual-level data from Latino participants diagnosed with CRC from California, Florida, and Puerto Rico. Biospecimens, epidemiologic data, and clinical outcomes were collected from each contributing study. DNA was extracted from tumor tissue and paired germline or normal tissue samples. Whole exome sequencing was performed using established protocols. Global genetic ancestry was estimated from whole exome sequence data. High-throughput T cell receptor (TCR) sequencing was used to estimate features of the T cell receptor (TCR) repertoire (e.g. abundance, clonality), and tumor-infiltrating lymphocyte (TIL) counts were obtained through pathology review. We evaluated differences in TCR abundance and TILs by sex using linear models for continuous measurements and generalized linear models for binary or count measurements. Primary analyses were unadjusted, and secondary analyses adjusted for age at diagnosis, stage at diagnosis, tumor location (right colon vs. left colorectum), and microsatellite instability (MSI) status. To examine how genetic ancestry modified the relationship between sex and T cell responses, we fit separate models with an interaction term between each genetic ancestry proportion variable (i.e. African, European, Native American) and sex, and assessed effect modification using a likelihood ratio test. Results: To date, 240 participants had TCR repertoire profiling and whole exome sequencing data generated. 52% were male, with a mean age of 58. 17% of participants had rectal tumors. With respect to Hispanic ethnic heritage or country of origin, 49% of participants were of Mexican descent, followed by 13% of Central or South American descent, and 10% were of Puerto Rican descent. Mean T cell abundance was 0.18 (standard deviation (SD): 0.16) and mean clonality was 0.05 (SD: 0.05). Further analysis is underway. Conclusions: This project leverages within-Latino genetic diversity to disentangle the contributions of sex and genetic ancestry to variability in immune function and to understand how this may further sex disparities in CRC. We anticipate that results from this analysis will provide insight on the relationship between the tumor immune microenvironment and sex disparities in CRC. Citation Format: Nicole C. Loroña, Ya-Yu Tsai, Daniel Sobieski, Eric Cockman, Stephanie L. Schmit, Jane C. Figueiredo. Examining the role of T cell responses in colorectal cancer sex disparities [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C156.