Fully human anti-B7-H4 antibody induces lysosome-dependent ferroptosis to reverse primary resistance to PD-1 blockade.

ABSTRACT:

Background

Although immune checkpoint inhibitors (ICIs) have significantly improved outcomes for patients with certain cancers, their efficacy is largely confined to "hot" tumors characterized by robust infiltration of tumor-specific CD8⁺ T cells. Conversely, tumors expressing B7-H4 often exhibit an immunologically "cold" tumor microenvironment with poor T cell infiltration, contributing to primary resistance to programmed cell death protein 1 (PD-1) blockade.

Methods

We evaluated the association between B7-H4 expression and clinical outcomes in ICI-treated patients using public immunotherapy datasets. The role of B7-H4 in mediating resistance to PD-1 therapy was examined in mouse tumor models. A fully human anti-B7-H4 monoclonal antibody (clone A8) was generated

SUBMITTER: Zhang R 

PROVIDER: S-EPMC12815153 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature