Targeting conserved TIM3⁺VISTA⁺ tumor-associated macrophages overcomes resistance to cancer immunotherapy.

ABSTRACT: Despite the success of immunotherapy, overcoming immunoresistance in cancer remains challenging. We identified a unique niche of tumor-associated macrophages (TAMs), coexpressing T cell immunoglobulin and mucin domain-containing 3 (TIM3) and V-domain immunoglobulin suppressor of T cell activation (VISTA), that dominated human and mouse tumors resistant to most of the currently used immunotherapies. TIM3⁺VISTA⁺ TAMs were sustained by IL-4-enriching tumors with low (neo)antigenic and T cell-depleted features. TIM3⁺VISTA⁺ TAMs showed an anti-inflammatory and protumorigenic phenotype coupled with inability to sense type I interferon (IFN). This was established with cancer cells succumbing to immunogenic cell death (ICD). Dying cancer cells not only t

SUBMITTER: Vanmeerbeek I 

PROVIDER: S-EPMC11259173 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature