Increased density of CD103-positive tissue-resident memory T cells predicts favorable response to immunotherapy in oral cancers

Abstract Immune checkpoint inhibitors (ICIs) have become an important therapeutic option for oral cancers; however, reliable biomarkers predicting treatment efficacy remain limited. In this study, we investigated the association between intratumoral immune cell subsets, regional lymph node (RLN) immune status, and clinical responses to ICIs in patients with recurrent oral cancer. Pretreatment tumor tissues and RLNs were analyzed by immunohistochemistry to evaluate tumor-infiltrating lymphocytes, including CD8 + , CD103 + , CD3 + , ICOS + , and CD163 + cells, as well as programmed death-ligand 1 (PD-L1) expression and CD169 + sinus macrophages. Treatment responses were assessed according to RECIST version 1.1. Responders to ICIs exhibited higher densities of CD8 + and CD103 + T cells compared with non-responders, whereas no significant associations were observed for CD3 + , ICOS + , CD163 + cells, or PD-L1 expression. Elevated pretreatment serum C-reactive protein (CRP) levels were associated with poorer responses. CD169 + sinus macrophages in RLNs did not correlate significantly with treatment efficacy or T-cell infiltration. These findings suggest that intratumoral effector and tissue-resident memory–like T-cell infiltration, together with systemic inflammatory status, may influence ICI efficacy in recurrent oral cancer, and could improve patient stratification for immunotherapy.