A pan-cancer single-cell transcriptional atlas of tumor infiltrating myeloid cells

TLDR

Tumor‑infiltrating myeloid cells are key regulators of tumor progression, yet their similarities and differences across cancers are poorly understood. The study performed a pan‑cancer single‑cell analysis of myeloid cells from 210 patients in 15 cancer types to identify distinct TIM features. The atlas revealed that mast cells in nasopharyngeal cancer correlate with better prognosis and an anti‑tumor phenotype, that LAMP3+ cDCs differ transcriptionally between cDC1 and cDC2 origins, that pro‑angiogenic TAMs display diverse markers across cancers, and that TIM composition associates with somatic mutations and gene expression, providing a heterogeneous landscape that informs future targeted immunotherapies.

Abstract

Tumor-infiltrating myeloid cells (TIMs) are key regulators in tumor progression, but the similarity and distinction of their fundamental properties across different tumors remain elusive. Here, by performing a pan-cancer analysis of single myeloid cells from 210 patients across 15 human cancer types, we identified distinct features of TIMs across cancer types. Mast cells in nasopharyngeal cancer were found to be associated with better prognosis and exhibited an anti-tumor phenotype with a high ratio of TNF+/VEGFA+ cells. Systematic comparison between cDC1- and cDC2-derived LAMP3+ cDCs revealed their differences in transcription factors and external stimulus. Additionally, pro-angiogenic tumor-associated macrophages (TAMs) were characterized with diverse markers across different cancer types, and the composition of TIMs appeared to be associated with certain features of somatic mutations and gene expressions. Our results provide a systematic view of the highly heterogeneous TIMs and suggest future avenues for rational, targeted immunotherapies.