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

Marceaux, C; Tarasova, I; Batey, D; Yokote, K; Gayevskiy, V; Jain, R; Leiwe, M; Choux, L; Riley, L; Ribera, NT; Yang, E; Hywood, J; Christie, M; Antippa, P; Speed, TP; Rogers, KL; Phipson, B; Asselin-Labat, ML

Author(s): Marceaux, C; Tarasova, I; Batey, D; Yokote, K; Gayevskiy, V; Jain, R; Leiwe, M; Choux, L; Riley, L; Ribera, NT; Yang, E; Hywood, J; Christie, M; Antippa, P; Speed, TP; Rogers, KL; Phipson, B; Asselin-Labat, ML;
Details: Publication Year 2026-02-17,Volume 7,Issue #2,Page 102593
Journal Title: Cell Reports Medicine
Abstract: The 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 phenotype. In lymphoid-enriched tumors, high infiltration of CD14(+)CD4(+) T cells correlates with poor patient survival. Spatial transcriptomics reveal enrichment of tumor necrosis factor alpha (TNF-alpha) signaling in CD14(+)CD4(+)-T-cell-rich tumors. Functional assays demonstrate that TNF-⍺ enhanced trogocytosis, promoting the formation of CD14(+)CD4(+) T cells. These findings uncover a TNF-⍺-mediated mechanism of immunosuppression in the TME and highlight aberrant myeloid-T cell interactions as contributors to NSCLC progression.
Publisher: Elsevier
Keywords: Humans; *CD4-Positive T-Lymphocytes/immunology/metabolism; *Tumor Necrosis Factor-alpha/metabolism; *Lipopolysaccharide Receptors/metabolism/immunology; *Lung Neoplasms/immunology/pathology/mortality; *Adenocarcinoma of Lung/immunology/pathology/mortality/genetics; Tumor Microenvironment/immunology; *Myeloid Cells/immunology/metabolism; Carcinoma, Non-Small-Cell Lung/immunology/pathology; Female; Tnf⍺; cell neighborhood; image mass cytometry; myeloid-instructed T cells; non-small cell lung cancer; spatial proteomics; spatial transcriptomics; trogocytosis; tumor microenvironment
Research Division(s): Personalised Oncology; Bioinformatics and Computational Biology; New Medicines and Diagnostics; Advanced Technology and Biology
PubMed ID: 41666923
Publisher's Version: https://doi.org/10.1016/j.xcrm.2026.102593
Open Access at Publisher's Site: https://doi.org/10.1016/j.xcrm.2026.102593
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2026-03-16 01:38:22

Last Modified: 2026-03-16 01:52:35