Discussion
PD, mTNBC, pembrolizumab-treated melanoma
PROLIFERATIVE, BREAST CANCER
Although limited by small sample size, the results of the current trial provide evidence that doxorubicin can be safely combined with pembrolizumab with Several studies have demonstrated utility of chemo-immunotherapy combination in treatment of mTNBC. FDA accelerated approval was granted to atezolizumab in March 2019 based on data from IMpassion130 trial (NCT02425891) which demonstrated a statistically significant benefit to PFS with the atezolizumab and nab-paclitaxel vs. nab-paclitaxel alone (HR, 0.60; 95% CI 0.48–0.77; Anthracyclines are among the most active agents for treatment of breast cancer. Anthracycline elicited immunogenic apoptosis in the preclinical setting [Our profiling of T cell dynamics in mTNBC patients treated with doxorubicin and pembrolizumab provides insight into immunotherapy response mechanisms. In this study, baseline immune biomarkers were not associated with response to treatment. In the patient with PD, significantly low levels of naïve CD8 + and CD4 + T cells at baseline indicating the presence of naïve CD8 + and CD4 + T cell is necessary for response to immune checkpoint blockade. Indeed, recent evidence has suggested that PD-1 blockade instills anti-tumor T cell immunity via the generation of non-preexisting T cell clonotypes [Importantly, we find that the expansion and not baseline percentages of proliferative exhausted CD8 + T cells that correlates with response to PD-1 blockade, which is in agreement with studies of pembrolizumab-treated melanoma patients [Increasing attention is now being turned toward understanding how existing cytotoxic chemotherapies generate or shape an immune response, and how these may best partner with immunotherapies [In conclusion, anthracycline-naïve patients with mTNBC treated with the combination of pembrolizumab and doxorubicin showed an encouraging response rate and robust T cell responses. The combination was generally well tolerated, and the utility of this combination needs to be further studied.