How Does Pembrolizumab Impact the Tumor Microenvironment of Triple-Negative Breast Cancer?
Posted: Monday, January 10, 2022
The phase Ib KEYNOTE-173 study, conducted by Peter Schmid, MD, PhD, of the Centre for Experimental Cancer Medicine, London, United Kingdom, and colleagues, evaluated the effects of the PD-1 inhibitor pembrolizumab on the tumor microenvironment of patients with triple-negative breast cancer. Presented during the 2021 Society for Immunotherapy of Cancer (SITC) Annual Meeting (Abstract 338), their results concluded that myeloid cell populations within the tumor at baseline demonstrated a “promising association trend” after neoadjuvant pembrolizumab and chemotherapy, despite the small sample size.
The study authors focused on 20 paired samples of triple-negative breast cancer that were obtained following one cycle of pembrolizumab but before chemotherapy initiation. Multiplex immunohistochemistry was performed to analyze deconvoluted cell fractions by spatial localization using T-cell, myeloid cell, and natural killer cell six-plex panels.
A total of 6 of 75 analyzed immune subsets demonstrated 95% confidence intervals of AUROC and did not cross 0.5 with pathologic complete response. This consisted of myeloid cell populations within the tumor compartment, specifically CD11c-positive (macrophage and dendritic cell [DC] = 0.85), CD11c-positive/MHC-II–positive/CD163-negative/CD68-negative (DC = 0.76), CD11c-positive/MHC-II–negative/CD163-negative/CD68-negative (immature/nonactivated DC = 0.8), and CD11c-positive/CD163-positive (M2 macrophage = 0.77) cells.
Baseline CD11c-positive/MHC-II–negative/CD163-negative/CD68-negative within the total tumor (AUROC = 0.76) and ratio of CD11c/CD3 within the tumor compartment (AUROC = 0.75) associated with pathologic complete response. Specific CD8 subsets, such as CD8-positive/granzyme B–positive/Ki67-positive, showed a weak trend toward association. Additionally, negative correlations between change from baseline-to-baseline values were observed. Of note, a negative association trend between change from baseline and pathologic complete response after baseline detrending was observed in CD163-positive/MHC-II–positive within the stroma (AUROC = 0.2).
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