Nectins: Orchestrating tumor progression and immune evasion.

Nectins and Nectin-like (Necl) proteins, a family of immunoglobulin-like cell adhesion molecules, are increasingly recognized for their dysregulated expression and aberrant functions in malignancies. They exert dual roles in cancer: promoting tumor progression (proliferation, invasion, metastasis, chemoresistance) through tumor-intrinsic and microenvironment-mediated mechanisms and facilitating immune evasion by engaging checkpoint receptors (TIGIT, CD96, PVRIG) on cytotoxic lymphocytes. Consequently, Nectins have emerged as critical therapeutic targets for modulating both tumor biology and the immune microenvironment. Recent therapeutic advances, particularly Nectin-4-targeted ADCs, anti-TIGIT ICIs, and bispecific antibodies (BsAbs), underscore their clinical promise. This review integrates current understanding of Nectin family members in oncogenesis and immunoregulation, focusing on their biological functions, mechanisms of immune modulation, therapeutic strategies, and remaining challenges in clinical translation.