Low initial levels of CD4+ Tregs, proliferating CD8+, and Granzyme B+ CD8+ T cells and high posttreatment tumor MHC class II expression predict better.

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Low initial levels of CD4+ Tregs, proliferating CD8+, and Granzyme B+ CD8+ T cells and high posttreatment tumor MHC class II expression predict better response to treatment. Low initial levels of CD4+ Tregs, proliferating CD8+, and Granzyme B+ CD8+ T cells and high posttreatment tumor MHC class II expression predict better response to treatment. A, Baseline percentages of CD4+ Treg of all T cells were gated (CD3+ CD4+ CD25+ CD127−) and visualized in tSNE space using Cytobank software. A low baseline percentage of CD4+ Tregs correlated to a better distal clinical response (P = 0.0209) by linear regression analysis. B, Baseline percentages of proliferating (Ki67+) CD8+ cells as a total of CD8+ T cells were gated and visualized in tSNE space. A lower percentage of proliferating CD8+ T cells correlated to better distal response (P = 0.0073) by linear regression analysis. C, Baseline percentage of Granzyme B+ (GzB) CD8+ cells as a total of CD8+ T cells were gated and visualized in tSNE space. A lower percentage of GzB+ CD8+ T cells correlated to better distal response (P = 0.0029) by linear regression analysis. D, Posttreatment (day 9) tumor cells were gated and visualized in tSNE space to evaluate MHC class II (HLA-DR) expression. Tumor cell MHC class II expression as measured by mean fluorescence intensity (MFI) positively correlated to distal response (P = 0.0390) by linear regression analysis. Each patient is tracked by a specific color. Matthew J. Frank et al. Cancer Discov 2018;8:1258-1269 ©2018 by American Association for Cancer Research