Harnessing gene fusion-derived neoantigens for ‘cold’ breast and prostate tumor immunotherapy

Abstract

Breast and prostate cancers are generally considered immunologically ‘cold’ tumors due to multiple mechanisms rendering them unresponsive to immune checkpoint blockade therapies. With little success in garnering positive outcomes in modern immunotherapeutic clinical trials, it is prudent to re-examine the role of immunogenic neoantigens in these cold tumors. Gene fusions are driver mutations in hormone-driven cancers that can result in alternative mutation-specific neoantigens to promote immunotherapy sensitivity. This review focuses on 1) gene fusion formation mechanisms in neoantigen generation; 2) gene fusion neoantigens in cancer immunotherapeutic strategies and associated clinical trials; and 3) challenges and opportunities in computational and liquid biopsy technologies. This review is anticipated to initiate further research into gene fusion neoantigens of cold tumors for further experimental validation.