Altered T-cell phenotype correlates with impaired adaptive vaccine response in patients in CR after DLBCL. (A-B) Analysis of total counts and fractions of indicated T-cell subpopulation measured by flow cytometry in HCs and patients with DLBCL in CR, when ND, or when R/R. Each symbol represents an individual patient, P values determined by ordinary 1-way ANOVA including 2-group comparison using Šidák multiple comparison when indicated. (C) Time point of individual CD4+ T-cell or of Tn cell measurement from panels A and B, respectively. The red lines indicate linear regression over time including 95% CI and slope. (D) CD4+ T cells or Tn cells of 27 patients were measured longitudinally and normalized to the first measurement. The red lines indicate linear regression over time including 95% CI and slope. (E) Rate of peripheral CD4+ Tn cell counts in regard to cell of origin (COO), revised international prognostic index (R-IPI), Ann Arbor stage, age, sex, or tumor bulk. Each symbol represents a single patient, P values determined by unpaired t tests. (F) Flow cytometry–based measurements of activated HLA-DR+/CD4+ or CD69+/CD4+ T cells. Each symbol represents individual patients, 2 group comparison by ordinary 1-way ANOVA using the Šidák multiple comparison. (G) After antigen-specific stimulation (SARS-CoV-2 peptides) of T cells from HCs or patients in CR, interferon-γ (IFN-γ) in the supernatant and intracellular IFN-γ in CD8+ T cells were compared. Significance was determined by unpaired t tests. (H) Correlogram of the ratio of cell subsets frequencies and anti-spike SARS-CoV-2 T-cell responses across vaccinated HCs and patients in CR. Colored circles represent correlations with P ≤ .05 as determined by the Spearman analysis. Blue and red circles indicate positive and negative correlations, respectively. Color intensity and the size of the circle are proportional to the correlation coefficients. (I) A PCA was performed among patients with DLBCL in CR combining all phenotypic myeloid and T-cell parameters from flow cytometry with HCs and patients with R/R disease mapped using a fixed parameter distribution. Although patients in CR show a diffuse pattern, indicating no clear separation among those patients, the respective HC and R/R clusters separate within the map. Large symbols indicate the centroids of the corresponding groups. For all panels, ∗P < .05; ∗∗P < .01; ∗∗∗P < .001; ∗∗∗∗P < .0001. Dim, dimension; GCB, germinal center B cell; MFI, mean fluorescence intensity; ns, not significant.