Tumor-associated macrophage clusters linked to immunotherapy in a pan-cancer census.
NPJ Precis Oncol
; 8(1): 176, 2024 Aug 09.
Article
in En
| MEDLINE
| ID: mdl-39117688
ABSTRACT
Transcriptional heterogeneity of tumor-associated macrophages (TAMs) has been investigated in individual cancers, but the extent to which these states transcend tumor types and represent a general feature of cancer remains unclear. We performed pan-cancer single-cell RNA sequencing analysis across nine cancer types and identified distinct monocyte/TAM composition patterns. Using spatial analysis from clinical study tissues, we assessed TAM functions in shaping the tumor microenvironment (TME) and influencing immunotherapy. Two specific TAM clusters (pro-inflammatory and pro-tumor) and four TME subtypes showed distinct immunological features, genomic profiles, immunotherapy responses, and cancer prognosis. Pro-inflammatory TAMs resided in immune-enriched niches with exhausted CD8+ T cells, while pro-tumor TAMs were restricted to niches associated with a T-cell-excluded phenotype and hypoxia. We developed a machine learning model to predict immune checkpoint blockade response by integrating TAMs and clinical data. Our study comprehensively characterizes the common features of TAMs and highlights their interaction with the TME.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
NPJ Precis Oncol
Year:
2024
Document type:
Article
Affiliation country:
China
Country of publication:
Reino Unido