The tumor microenvironment in triple negative breast cancer and a strategy to improve responses to immunotherapy using cryoablation and immunostimulants

One in eight women will develop breast cancer (BC) over their lifetime. Triple-negative breast cancer (TNBC) accounts for up to 20% of BC cases and has fewer treatment options, greater metastatic potential, a higher risk of recurrence, and a poorer prognosis compared to other BC subtypes. Compared to hormone receptor-positive BCs, TNBC has more tumor-infiltrating lymphocytes, a higher tumor mutational burden, and greater programmed death ligand-1 (PD-L1) expression. While these features suggest greater immunogenicity, the balance of the complex TNBC tumor microenvironment (TME) is immunosuppressive. The TME leads to modest and variable effects of immune checkpoint inhibitors (ICI) for TNBC. This review explores the dysfunctional immunological state of TNBC and proposes a multi-modal strategy integrating cryoablation as a source of tumor-associated antigens (TAAs) and immunostimulatory agents to reprogram antitumor immunity. It specifically explores the strategy of combining ICI and immunostimulants with cryoablation as a source of TAAs.