From lactation to tumor immune modulation: emerging roles of prolactin in regulating tumor antigen presentation in breast cancer 3235

Abstract Description Tumor antigen presentation is essential for anti-tumor immunity, with therapies like mRNA and Tecelra relying on effective antigen presentation. Understanding factors that influence this process could improve current treatments. Prolactin, a hormone secreted by tumor cells, plays a role in tumor progression, but its impact on tumor immunity remains unclear. This study investigates prolactin’s effect on tumor antigen presentation and immune responses. Using a co-culture system of mouse dendritic cells and aggressive breast cancer cell lines (EO771 and Py230), we found that prolactin reduced tumor antigen phagocytosis and downregulated key genes involved in antigen processing and presentation, including MHC I/II, TAP1/2, ERp57, and CD80. Prolactin also decreased tumor antigen presentation via MHC I and II on dendritic cells. In an in vivo syngeneic mouse model with 4T1 TNBC cells, systemic knockdown of the prolactin receptor (LFPRLR) restored antigen presentation, increasing CD80 expression on dendritic cells and macrophages, reducing PD-L1, and activating CD4+ and CD8+ T cells. Our findings reveal a novel role for prolactin in inhibiting immune cell antigen presentation within the tumor microenvironment, suggesting that targeting PRLR signaling could enhance anti-tumor immunity. Funding Sources This research is supported by NIGMS (GM153648-01), NCI (CA 293129), and Texas Tech University new faculty startup to KuanHui E. Chen. Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)