SLAMF7 improves the efficacy of PD-1 immunotherapy by enhancing T cell response in non-small cell lung cancer.

Programmed death-1 (PD-1) immune checkpoint inhibition has transformed the therapeutic landscape of non-small cell lung cancer (NSCLC), while a proportion of NSCLC cases exhibited primary or acquired resistance, reflecting the imperative to elucidate resistance mechanisms and identify synergistic immunomodulatory targets. In this context, strategies that augment the functional competence of effector T cells represent an important direction for improving immunotherapeutic efficacy. This study sought to characterize the immunological role of signaling lymphocytic activation molecule family member 7 (SLAMF7) in modulating T cell-mediated responses in non-small cell lung cancer (NSCLC). Peripheral T cells from NSCLC cases exhibited an escalated SLAMF7 expression level relative to healthy controls. Furthermore, this upregulation was more pronounced in patients who demonstrated clinical responsiveness to anti-PD-1 therapy. Moreover, SLAMF7 expression level demonstrated a positive link with both T cell abundance and the frequencies of cytokine-secreting T cell subsets. Mechanistic insights derived from a murine lung carcinoma model confirmed these outcomes. SLAMF7-deficient mice exhibited impaired anti-tumor immunity, as evidenced by accelerated tumor progression and attenuated effector cytokines production. Conversely, therapeutic co-engagement of SLAMF7 via recombinant SLAMF7 (rm-SLAMF7) plus PD-1 blockade significantly amplified anti-tumor responses, characterized by enhanced T cell expansion, activation, and cytotoxic potential. Consequently, these outcomes suggested that targeting SLAMF7 may offer a strategy to enhance PD-1-directed immunotherapy in NSCLC.