LAUSR

Mast cells constitute indispensably immunoregulatory sentinel cells in tumor microenvironment, however, their functions are poorly characterized in lung adenocarcinoma (LUAD). Here, we performed flow cytometry and single-cell RNA sequencing to comprehensively characterize LUAD infiltrating MCs. MCs exhibited remarkably functional heterogeneity and were enriched in ground-glass opacity featured LUAD (gLUAD). The MCs in gLUAD exhibited proinflammatory and chemotactic properties while the MCs in radiologically solid LUAD (sLUAD) were associated with tumor angiogenesis. MCs were an important source of CCL2 that correlated with the recruitment of CCR2+ cytotoxic T lymphocytes (CTLs), which represent a specific subcluster of pre-exhausted T cells with tissue-resident memory phenotype and enhanced cytotoxicity. Increased infiltration of MCs-CCR2+ CTLs and their colocalization showed a strong association with favorable prognosis after surgery but were not associated with improved survival after chemotherapy. Collectively, these findings reveal a key role of MCs in LUAD and their potential crosstalk with CTLs, suggesting that targeting MCs may be a novel immunotherapeutic strategy for LUAD. Citation Format: Fan Fan, Xiaoming Zhang, Haiquan Chen. Enhanced mast cell abundance is associated with the enrichment of CCR2+ cytotoxic T cells and favorable prognosis in lung adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5940.