Multitumor Case Series of Germline <i>BRCA1</i>, <i>BRCA2</i> and <i>CHEK2</i>-Mutated Patients Responding Favorably on Immune Checkpoint Inhibitors

Abstract

In recent years, immune checkpoint inhibitors (ICPI) have become widely used for multiple solid malignancies. Reliable predictive biomarkers for selection of patients who would benefit most are lacking. Several tumor types with somatic or germline alterations in genes involved in the DNA damage response (DDR) pathway harbor a higher tumor mutational burden, possibly associated with an increased tumoral neoantigen load. These neoantigens are thought to lead to stronger immune activation and enhanced response to ICPIs. We present a series of seven patients with different malignancies with germline disease-associated variants in DDR genes (BRCA1, BRCA2, CHEK2) responding favorably to ICPIs.

Keywords

• DNA damage response
• immune checkpoint inhibitors
• <i>BRCA1</i>
• <i>BRCA2</i>
• <i>CHEK2</i>