B-cell checkpoint AH004 (AH004)

AH004 is a novel B-cell checkpoint protein identified as a key driver of adaptive resistance to immune checkpoint inhibitors, particularly anti-PD1 therapy in melanoma. It is a cell-surface receptor expressed on B-cells that functions by inhibiting the effector activities of T cells and natural killer (NK) cells, thereby fostering an immunosuppressive tumor microenvironment. Research presented at the AACR Annual Meeting 2026 demonstrated that AH004 is differentially regulated in approximately 17% of patients who do not respond to standard-of-care immunotherapy. Tumors expressing AH004 often exhibit a "pseudohot" phenotype, characterized by an inflamed but ineffective immune response. Therapeutic strategies involving the blockade of AH004 using monoclonal antibodies are being developed to intercept this resistance mechanism and extend the clinical benefit of existing immunotherapies.

Other names

B-cell checkpoint AH004Apricity Health AH004

Blockade of AH004 to restore T and NK cell activity and overcome adaptive resistance to anti-PD1 therapy