Abstract C118: Modulation of Prostate Cancer Microenvironment and Immune Responses by SPDEF

Abstract Introduction: The prostate cancer (PCa) microenvironment plays a pivotal role in modulating immune responses, potentially impacting disease progression and treatment outcomes. SPDEF, a transcription factor, has been implicated in PCa progression, yet its influence on the tumor immune microenvironment remains incompletely understood. Methods: To comprehensively evaluate the impact of SPDEF-mediated changes in the PCa microenvironment on immune cells, we employed multiple experimental approaches. Firstly, utilizing the ProcartaPlex Human Cytokine & Chemokine Panel 1 16plex assay, we analyzed cytokine and chemokine alterations in cell culture supernatants from various PCa cell line models—PC3-VC, PC3-SPDEF, RC77/T-VC, RC77/T-SPDEF, LNCaP-VC, and LNCaP-shSPDEF. Subsequently, human primary T cells were exposed to PCa cell-derived conditioned media to assess their proliferation and activation status, using IncuCyte cell imaging and flow cytometry, respectively. Results: Our ProcartaPlex assay validated transcriptomic observations from RNA-seq experiment, confirming elevated cytokine/chemokine levels in SPDEF-overexpressing models and decreased levels in SPDEF-suppressed conditions. Notably, T cell proliferation assays demonstrated increased proliferation in response to SPDEF-overexpressing PCa conditional media and diminished proliferation in SPDEF-suppressed conditions. Moreover, SPDEF downregulation led to decreased proliferation in both CD4+ and CD8+ T cells. Assessing CD8+ T cell activation markers revealed varying impacts on IFN-γ expression, showing reduced levels in LNCaP-shSPDEF but inconclusive effects in PC3-SPDEF overexpression models. Conclusions: These findings highlight the complex interplay between SPDEF alterations in the PCa microenvironment and immune cell behavior, particularly T cell proliferation and activation. The observed effects underscore the complexity of SPDEF-mediated alterations on immune responses within the tumor milieu. Further investigations into the divergent effects of SPDEF on T cell dynamics are warranted to elucidate the precise mechanisms governing these interactions, potentially offering insights into novel therapeutic targets for PCa. Citation Format: Mousa K. Vatanmakanian, Maria Sanchez-Pino, Guanyi K. Zhang, Sweaty Koul, Ramesh T. Puttalingaiah, Mathew Dean, Dorota K. Wyczechowska, Augusto Ochoa, Hari K Koul. Modulation of Prostate Cancer Microenvironment and Immune Responses by SPDEF [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 C118.