Abstract A058: Evaluation of <i>KLRC2</i> deletion in a racially diverse cohort of prostate cancer patients

Abstract Background: Natural Killer (NK) cells play a vital role in anti-tumor immunity through direct tumor cell lysis. Recent studies indicate immune microenvironment differences in prostate tumors between African American (AA) and Caucasian American (CA) men; however, the contribution of NK cell-associated genes to these disparities remains incompletely understood. The NK cell receptor gene, KLRC2, is of particular intertest, as prior work from our group demonstrated significantly lower KLRC2 expression in AA prostate tumors compared to CA tumors. Given that germline KLRC2 deletion polymorphisms differ across global populations, including East and West African ancestry groups, investigating its deletion status may provide insight into downstream expression differences and associated immune variation. Purpose: The purpose of this study was to gain a deeper understanding of immunobiological differences between AA and CA men with prostate cancer (PCa) by evaluating an NK cell-relevant gene, KLRC2, in racially diverse genomic datasets. We hypothesized that germline deletion may contribute to its variability in downstream expression and ultimately contribute to observed racial disparities in PCa. Methods: We analyzed germline whole genome sequencing data from a large Center for Prostate Disease Research (CPDR) cohort matched for AA (n=259) and CA (n=272) men. Bioinformatics workflows were applied to accurately infer KLRC2 deletion status, including copy-number calling and quality control filtering. Results: We identified a significant difference in the heterozygous deletion status of KLRC2 between AA and CA men in this robust CPDR cohort. These findings suggest population-level variation in KLRC2 copy number that may account for reduced KLRC2 expression previously observed in AA prostate tumors. Conclusions: Germline deletions in the KLRC2 gene may contribute to alterations in NK cell-mediated immune function in the tumor microenvironment of AA men with PCa. Our findings provide foundational evidence that KLRC2 status may play a role in racial immune disparities and highlight KLRC2 as a potential biomarker and candidate target for NK cell-based immunotherapeutic strategies. Conflict of Interest Disclaimer Statement: The contents of this publication are the sole responsibility of the author(s) and do not necessarily reflect the views, opinions or policies of Uniformed Services University of the Health Sciences (USUHS), the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., the Department of War (DoW) or the Departments of the Army, Navy, or Air Force. Mention of trade names, commercial products, or organizations does not imply endorsement by the U.S. Citation Format: Laila N. Scroggins, Paula O. Cooper, Stefan DiFazio, Kun L. Ho, Ayesha A. Shafi, Cara Schafer. Evaluation of KLRC2 deletion in a racially diverse cohort of prostate cancer patients [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Innovations in Prostate Cancer Research and Treatment; 2026 Jan 20-22; Philadelphia PA. Philadelphia (PA): AACR; Cancer Res 2026;86(2_Suppl):Abstract nr A058.