Fig. 4
Anti-human epidermal growth factor receptor 2 (anti-HER2) CD4+ T-helper type-1 (Th1) is the dominant phenotype contributing to interferon-γ+ (IFN-γ +) CD4 + T cell deficit in patients without pathologic complete response (non-pCR). a Relative contributions of Th1 (T-bet + IFN-γ +) versus Th2 (GATA-3 + IFN-γ +) phenotypes to HER2 peptide-specific IFN-γ+ cells in peripheral blood mononuclear cells (PBMC) from pCR and non-pCR patients. Representative stains within groups are shown after gating on CD4+ cells; results in adjoining histograms are expressed as mean proportions (%) ± standard error of the mean (SEM) as indicated. b Circulating HER2-specific IL-4 production does not vary between pCR and non-pCR patients, when assessed by responsivity, repertoire, and cumulative response. Results expressed as proportion or mean ± SEM (top panel). Donor-matched cumulative IFN-γ and IL-4 production (spot-forming cells (SFC)/106 cells) across six HER2 class II peptides compared in pCR and non-pCR patients. Relative HER2-specific IFN-γ:IL-4 proportions (% depicted in graph) was significantly higher in pCR (IFN-γ/(IFN-γ + IL-4) = 73.9 %:IL-4/(IFN-γ + IL-4) = 26.1 %) compared with non-pCR patients (34.6 %:65.4 %). Absolute IFN-γ:IL-4 production ratio changed from 2.8:1 (pCR) to 0.5:1 (non-pCR) (bottom left panel). No relative shifts in IFN-γ:IL-4 production were observed to positive controls (anti-CD3/CD28 or anti-CD3, respectively) (bottom right panel). c HER2-specific IL-10 production is similar between pCR and non-pCR patients across all Th1 metrics. Results are expressed as proportion or mean ± SEM (top panel). Relative HER2-specific IFN-γ:IL-10 production was significantly higher in pCR (62.0:38.0 %) compared with non-pCR (23.8:76.2 %) patients. Absolute IFN-γ:IL-10 production ratio changed from 1.6:1 (pCR) to 0.3:1 (non-pCR) (bottom left panel). No relative shifts in IFN-γ:IL-4 production were observed to positive controls (anti-CD3/CD28 or anti-CD3, respectively) (bottom right panel); *p <0.05, ** p <0.01, *** p <0.001