CD4+ T Cells Mediate MHC-Deficient Tumor Rejection and Endothelial Cell Reprogramming.

ABSTRACT: Low or absent expression of MHC on tumor cells is a presumed mechanism of resistance to immunotherapy, but evidence for this has largely been indirect. Likewise, whether immunotherapy can be effective without tumor MHC expression is also poorly understood. Using genetically engineered mouse tumor cells expressing the model neoantigen ovalbumin, we found that MHC class I-deficient tumor cells, but not MHC class I-sufficient tumor cells, grew progressively when injected subcutaneously into syngeneic C57BL/6 mice. However, combination immunotherapy using agonistic anti-CD40 and dual immune checkpoint blockade (anti-PD-1 and anti-CTLA-4) was equally effective against tumors that did not express the MHC class I H-2Kb allele, MHC class II, or IFNγ receptor across multiple pancreatic tumor lines

SUBMITTER: Kim SI 

PROVIDER: S-EPMC12646680 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature