In their recent work published in Communications Biology and Cancers, Dr. Alyssa Vito and Dr. Karen Mossman propose a combination platform using low dose chemotherapy with oncolytic virotherapy and immune checkpoint blockade as a treatment regimen for triple negative breast cancer. They further identified a potential role of B cells in enabling an anti-cancer response via regulation of immunosuppressive myeloid cells.
Triple negative breast cancer has an immunologically cold tumor phenotype, which is notoriously difficult to treat in the clinic and is associated with poor patient survival. This breast cancer type also lacks expression of known surface targets, hence there are currently no targeted treatments available. Despite aggressive chemotherapy treatment regimes, relapse is common. As a result, new approaches for the treatment of triple negative breast cancer are urgent.
Using a mouse model of triple negative breast cancer, Vito et al. found that combination of low-dose chemotherapy (FEC) and an oncolytic virotherapy (oHSV-1) platform, developed in their lab, increased murine survival and delayed tumour growth. When they included a checkpoint inhibitor in their cocktail, the tumours showed significant regression and no signs of resistance to the combinatorial approach. The combination of FEC + oHSV-1 with the checkpoint inhibitor also increased the number of tumour-infiltrating B cells. Increased presence of B cells in tumours was correlated with a reduced number of myeloid derived suppressor cells, which contribute to the immunosuppressive tumour microenvironment.
Follow up work recently published in Cancers, demonstrated an increase in circulating inflammatory monocytes and macrophages following treatment with FEC + oHSV-1. Further, Vito et al. found an increase in the expression of S100A8 and S100A9, proteins associated with myeloid differentiation, in peripheral blood derived M1-like macrophages following combination treatment. Analysis of mRNA expression of S100A8 and S100A9 in breast cancer patients treated with FEC suggest that expression of S100A8/A9 are positive predictors of treatment response.
This research highlights the benefit of using a combination of immunotherapies to induce a hot tumour microenvironment which sensitizes tumours to treatment by checkpoint inhibitors. It also emphasized the importance of tumour-infiltrating B cell populations in antitumour immunity and in the regulation of the tumour microenvironment. Based on their findings, Vito et al. suggest that B cells should be investigated as potential biomarkers for predicting prognostic outcomes for different immunotherapies targeting solid tumors such as triple negative breast cancer.
Read the full articles here: