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Macrophage repolarization by immune checkpoint blockade drives T-cell engagement in the tumor microenvironment

ABSTRACT: Immunotherapy combinations can improve patient outcomes, yet the interactions within the tumor microenvironment (TME) that drive therapeutic synergy are poorly understood. Tumor establishment drives monocyte recruitment and differentiation into tumor-associated macrophages (TAMs), which have essential roles in coordinating immune responses and are thus attractive targets for therapeutic modulation. In a murine model of combination anti-PD-1 and anti-PD-L1 checkpoint blockade, tumor control was associated with increased infiltration of CD8+ T-cells and M1-like repolarization of TAMs. Live-cell imaging of the tumor microenvironment revealed close contacts between tumor-infiltrating CD8+ T-cells and TAMs, in which the extent of the contact interfaces increased with combination immunotherapy. Treatment with anti-PD-L1 was able to increase macrophage expression of pro-inflammatory factors and phagocytic activity, suggesting a role for TAMs in reactivating CD8+ T-cells in the TME. However, co-treatment with anti-PD-1 was ultimately necessary for tumor control, indicating the need for combination targeting of the TME.

ORGANISM(S): Mus musculus

PROVIDER: GSE305308 | GEO | 2025/12/02

REPOSITORIES: GEO

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