Radiation-induced SLAMF1 reconfigures the SLAM family receptors landscape in triple-negative breast cancer cells.

Abstract

Radiation therapy is a powerful immunomodulator capable of transforming the tumor microenvironment (TME). Signaling Lymphocytic Activation Molecule Family Member 1 (SLAMF1) is a cell surface receptor involved in various immune functions and cancer progression by regulating interactions with the immune microenvironment. However, the specific role of radiation in modulating the SLAM family within tumor cells remained poorly understood. Ionizing radiation markedly increased the expression of SLAM family, including SLAMF1, and other immune checkpoints in three triple-negative breast cancer (TNBC) cell lines by flow cytometry analysis. Furthermore, dual immunofluorescence staining of breast cancer patient tissues confirmed that SLAMF1 is localized to tumor site independently of immune cells. Interestingly, SLAMF1 overexpression in TNBC cells distinctively reconfigures the expression of SLAMF2 and SLAMF5, both linked to immunosuppressive signaling. These findings suggest a potential mechanism where radiation-induced SLAMF1 influences tumor immunogenicity by remodeling the inhibitory SLAM receptors landscape, potentially rendering tumor cells more susceptible to immune-mediated attack. As the first study to demonstrate endogenous SLAMF1 as a novel radiation-responsive factor in breast cancer, these results provide key insights for developing combined radiotherapy and immunotherapy strategies for TNBC.