Small Molecule Modulation of MHC-I Surface Expression: A Click Chemistry-Based Discovery Approach.

ABSTRACT: Immunotherapy has emerged as a powerful strategy for combating cancer by harnessing the patient's immune system to recognize and eliminate malignant cells. Major histocompatibility complex class I (MHC-I) plays a pivotal role by presenting neoantigens to CD8+ T cells, triggering T cell-mediated killing. However, cancer cells often evade detection by downregulating the MHC-I surface expression, hindering the immune response. This resistance mechanism offers an opportunity to bolster MHC-I surface expression via therapeutic interventions. We conducted a comprehensive evaluation of previously purported small molecule MHC-I inducers and identified heat shock protein 90 inhibitors as privileged enhancers. Using a core scaffold, we employed an in situ click chemistry-based derivatization strateg

SUBMITTER: Newkirk SE 

PROVIDER: S-EPMC12621194 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature