TNF-⍺-mediated myeloid-instructed CD14 CD4 T cells are associated with poor survival in lung adenocarcinoma

Abstract

SummaryThe tumor microenvironment is composed of diverse immune populations that can either support anti-tumor immunity or promote tumor progression. Myeloid cells are major drivers of immunosuppression, yet therapies targeting them have shown limited success. To uncover mechanisms underlying myeloid-driven immune suppression, we performed spatial multi-omics analyses of non-small cell lung cancer (NSCLC). Independent of oncogenic driver status, tumors stratify into lymphoid-enriched, myeloid-enriched, and mixed immune-infiltrated subtypes. In tumor and adjacent non-malignant lungs, we identify myeloid-instructed CD14+CD4+ T cells. These cells arise through trogocytosis adopting an atypical ..