Table 1.

Univariate and multivariate survival analyses for immune-checkpoint expression in DLBCL evaluated by percentage within a cell type

Univariate analysisMultivariate analysis for OSMultivariate analysis for PFS
Cutoff definition; prevalenceImpact in overall DLBCLImpact in T-cell–infiltrated DLBCLHR (95% CI)PHR (95% CI)P
PD-1 expression in a T-cell subtype
PD-1hi in CD8+ T cellsPD-1hi: ≥54.8% of CD8+ T cells; 29.1%Poorer OS: P = 0.0052; poorer PFS: P = 0.024Poorer OS: P = 0.0002; poorer PFS: 0.0023 in CD8+ patients1.93 (1.25–2.98)0.0031.67 (1.11–2.52)0.013
PD-1+ in CD4+ T cellsPD-1+: ≥3.0% of CD4+ T cells; 93.1%Poorer OS: P = 0.0025; poorer PFS: P = 0.0079Poorer OS: P = 0.0016; poorer PFS: P = 0.003 in CD4+ patients2.98 (1.20–7.39)0.0182.97 (1.09–8.09)0.033
PD-L1 expression in a specific cell type
PD-L1hi in B cellsPD-L1hi: ≥40% of CD20+ cells; 8.3%Better OS: P = 0.034 (P = 0.067 for better PFS)Better OS: P = 0.037 (P = 0.084 for better PFS) in CD3+ patients0.38 (0.15–0.93)0.0350.55 (0.27–1.12)0.099
In patients with PD-1loCD8+ T cells: prevalence, 10%Better OS: P = 0.032; better PFS: P = 0.04Better OS: P = 0.035; better PFS: P = 0.053 in CD3+ patients0.26 (0.08–0.83)0.0230.39 (0.16–0.96)0.04
Proximity between PD-L1+CD20+ B cells and PD-1+CD8+ T cellsIn patients with PD-1loCD8+ T cells: prevalence, 72.3%Better OS: P < 0.0001; better PFS: P < 0.0001Better OS: P = 0.0001; better PFS: P = 0.0033 in CD3+ patients0.35 (0.20–0.60)<0.0010.40 (0.24–0.67)<0.001
PD-L1+ in CD68+ cellsPD-L1+: ≥27% of CD68+ cells; 72.7%Poorer OS: P = 0.02 (P = 0.16 for PFS)Poorer OS: P = 0.015 (P = 0.14 for PFS) in CD3+ patients1.49 (0.93–2.40)0.0971.27 (0.83–1.93)0.27
In patients with PD-1hiCD8+ T cells: prevalence, 75.4%Poorer OS: P = 0.0052; poorer PFS: P = 0.024Poorer OS: P = 0.01; poorer PFS: P = 0.05 in CD8+ patients3.36 (1.18–9.56)0.0232.35 (0.97–5.67)0.058
PD-L1+ in T cellsPD-L1+: ≥5.8% of T cells; 27.4%Poorer OS: P = 0.04 (P = 0.16 for PFS)Poorer OS: P = 0.009 (P = 0.07 for poorer PFS) in CD3+ patients1.48 (0.98–2.23)0.0621.37 (0.93–2.02)0.12
PD-L1+ in NK cellsPD-L1+: ≥13.3% of NK cells; 41.2%Poorer OS: P = 0.038 (P = 0.069 for poorer PFS)Poorer OS: P = 0.0078; poorer PFS: P = 0.019 in CD3+ patients1.24 (0.86–1.80)0.261.36 (0.96–1.93)0.087
In patients with PD-1hiCD8+ T cells: prevalence, 49.2%Poorer OS: P = 0.0086; poorer PFS: P = 0.0029Poorer OS: P = 0.0066; poorer PFS: P = 0.0027 in CD8+ patients2.58 (1.30–5.11)0.0072.51 (1.34–4.71)0.004
PD-L2 expression in a specific cell type
PD-L2+ in B cellsPD-L2+: ≥25% of CD20+ cells; 5.2%Better OS: P = 0.0018; better PFS: P = 0.0018Better OS: P = 0.0039; better PFS: P = 0.0046 in CD3+ patients0.960.96
CTLA-4 expression in a T-cell subtype
CTLA-4+ in TregsCTLA-4+: ≥13% of Tregs; 15.8%Better OS: P = 0.018 (P = 0.098 for PFS)Better OS: P = 0.023 (P = 0.16 for PFS) in CD4+ patients0.45 (0.25–0.82)0.0090.49 (0.27–0.88)0.018
CTLA-4+ in conventional Th cellsCTLA-4+: ≥1.9% of Th cells; 22.0%Better OS: P = 0.023; better PFS: P = 0.039Better OS: P = 0.02; better PFS: P = 0.036 in CD4+ patients0.58 (0.36–0.95)0.0310.58 (0.35–0.94)0.027
  • NOTE: For multivariate survival analyses, Cox models were used and the factors included high International Prognostic Index score, sex, B-symptoms, >5-cm tumor size, and individual immune-checkpoint expression. For PD-1/PD-L1 expression in T cells, analyses were performed in patients with T-cell infiltration. For expression in other cell types, analyses were performed in the overall DLBCL cohort.

  • Significant P values are in bold.

  • Abbreviations: HR, hazard ratio; CI, confidence interval; NK, natural killer, CD56+CD3; Th, helper T cells, CD3+CD4+FOXP3 cells; Tregs, regulatory T cells, CD3+CD4+FOXP3+ cells.