Despite impressive durable responses, immune checkpoint inhibitors do not provide a long-term benefit to the majority of patients with cancer. Understanding genomic correlates of response and resistance to checkpoint blockade may enhance benefits for patients with cancer by elucidating biomarkers for patient stratification and resistance mechanisms for therapeutic targeting. Here we review emerging genomic markers of checkpoint blockade response, including those related to neoantigens, antigen presentation, DNA repair, and oncogenic pathways. Compelling evidence also points to a role for T cell functionality, checkpoint regulators, chromatin modifiers, and copynumber alterations in mediating selective response to immune checkpoint blockade. Ultimately, efforts to contextualize genomic correlates of response into the larger understanding of tumor immune biology will build a foundation for the development of novel biomarkers and therapies to overcome resistance to checkpoint blockade.

Immune checkpoint inhibitors (ICIs) have led to durable clinical remissions in many metastatic cancers. However, the single-agent efficacy of ICIs in breast cancer is low, including in triple-negative breast cancer (TNBC), which has several key characteristics that enhance ICI responses. Strategies to improve anticancer immune responses in TNBC are urgently needed to extend survival for patients with metastatic disease. This review presents ICI monotherapy response rates and discusses combination strategies with chemotherapy, targeted therapies, and novel immunotherapies. It concludes with a summary of immunotherapy biomarkers in TNBC and a call to action for future directions of research critical to advancing the efficacy of immunotherapy for patients with TNBC.Although response rates to ICIs are higher in TNBC than in hormone receptor-positive and HER2-positive breast cancers, the single-agent efficacy is still low, with monotherapy response rates ranging from approximately 5% in