TREM2 deficiency reprograms intestinal macrophages and microbiota to enhance anti-PD-1 tumor immunotherapy.
Sci Immunol
; 9(95): eadi5374, 2024 May 17.
Article
in En
| MEDLINE
| ID: mdl-38758808
ABSTRACT
The gut microbiota and tumor-associated macrophages (TAMs) affect tumor responses to anti-programmed cell death protein 1 (PD-1) immune checkpoint blockade. Reprogramming TAM by either blocking or deleting the macrophage receptor triggering receptor on myeloid cells 2 (TREM2) attenuates tumor growth, and lack of functional TREM2 enhances tumor elimination by anti-PD-1. Here, we found that anti-PD-1 treatment combined with TREM2 deficiency in mice induces proinflammatory programs in intestinal macrophages and a concomitant expansion of Ruminococcus gnavus in the gut microbiota. Gavage of wild-type mice with R. gnavus enhanced anti-PD-1-mediated tumor elimination, recapitulating the effect occurring in the absence of TREM2. A proinflammatory intestinal environment coincided with expansion, increased circulation, and migration of TNF-producing CD4+ T cells to the tumor bed. Thus, TREM2 remotely controls anti-PD-1 immune checkpoint blockade through modulation of the intestinal immune environment and microbiota, with R. gnavus emerging as a potential probiotic agent for increasing responsiveness to anti-PD-1.
Full text:
1
Database:
MEDLINE
Main subject:
Membrane Glycoproteins
/
Receptors, Immunologic
/
Programmed Cell Death 1 Receptor
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Gastrointestinal Microbiome
/
Immunotherapy
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Macrophages
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Mice, Inbred C57BL
Limits:
Animals
Language:
En
Journal:
Sci Immunol
/
Sci. immunol
/
Science immunology
Year:
2024
Type:
Article
Affiliation country:
United States