Abstract
The clinical response to immune checkpoint blockade (ICB) is limited in the majority of patients with colorectal cancer. These immune checkpoint proteins may not only inhibit T-cell-mediated antitumor immunity but also attenuate antigen presentation, including mutation-associated neoantigens. Here, we found that tumor B7-H3 levels may limit the therapeutic response to chemoradiotherapy in patients with locally-advanced rectal cancer. Knockdown of tumor B7-H3 significantly increased antigen presentation to increase T cell infiltration and killing ability, including neoantigen-specific T-cell response. Blockade of B7-H3 significantly augmented neoantigen-specific T cells response and remarkably enhanced the therapeutic efficacy of neoantigen-based cancer vaccines combined with radiotherapy, decreasing the risk of distant tumors in vivo. Taken together, these results demonstrated that targeting B7-H3 significantly enhanced the therapeutic efficacy of neoantigen cancer vaccines as well as radiotherapy by increasing the extent of neoantigen-specific T cells, even for PD-1/PD-L1 blockade-resistant colorectal cancers.