Harnessing Inflammatory Monocytes to Overcome Resistance to Anti-PD-1 Immunotherapy.

ABSTRACT:

Background

Resistance to immune checkpoint inhibitors represents a major therapeutic challenge, as less than 50% of patients with melanoma achieve long-term response to immune checkpoint inhibitor therapy. One mechanism of acquired resistance involves somatic mutations, such as loss of beta-2 microglobulin (B2m), that enable tumor cells to evade T cell-mediated killing.

Methods

This study used single-cell RNA-seq, flow cytometry, and ex vivo functional assays to characterize tumor-infiltrating immune cells in antigen presentation-deficient tumors. Tumor-bearing mice were treated with anti-PD-1 or CD40 agonist antibodies and cell depletion or cytokine blocking antibodies to define mechanisms of action. Analysis of published human RNA-seq datasets was performed to dissect the

SUBMITTER: Zimmerman MP 

PROVIDER: S-EPMC12889677 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature