Knockdown of MAP7D2 regulates the immune-modulatory function mediated by CD8+ T cells and inhibits LUAD progression

Tumor progression in lung adenocarcinoma (LUAD) is critically mediated by immune escape mechanisms. MAP7D2 was found to be upregulated in LUAD and associated with poor prognosis; however, its functional role in LUAD remains elusive.

Stable MAP7D2-knockdown cell lines were generated via lentiviral delivery of shRNA in human LUAD cell lines (A549 and NCI-H1648) and murine Lewis lung carcinoma cells. Immunocompetent syngeneic mouse models were established to evaluate the impact of MAP7D2 deficiency on tumor growth and antitumor immunity.

MAP7D2 silencing did not alter the intrinsic proliferative capacity or clonogenic potential of A549 and NCI-H1648 cells in vitro. Additionally, co-culture assays demonstrated that MAP7D2 knockdown in LLC cells significantly potentiated CD8⁺ T cell-mediated cytotoxicity. Concordantly, CD8⁺ T cells exhibited elevated IFN-γ expression and diminished PD-1/TIGIT expression, consistent with augmented effector function. In immunocompetent syngeneic mouse models, MAP7D2 knockdown significantly inhibited LLC tumor growth, which was mechanistically linked to increased intratumoral infiltration of CD8⁺ cytotoxic T lymphocytes. Mechanistically, the effects of MAP7D2 overexpression were reversed by HMGB1, restoring CD8⁺ T cell cytotoxicity.

MAP7D2 knockdown inhibited the growth and development of LUAD by increasing the infiltration of CD8⁺ T lymphocytes, thereby enhancing antitumor immunity.