A All patients Arm A Arm B Deaths/patients 21/30 7/10 14/20

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A All patients Arm A Arm B Deaths/patients 21/30 7/10 14/20 Median, months 16.2 15.6 1-year OS (%) 56.7 50 60 2-year OS (%) 43.3 40 45 3-year OS (%) 36.7 30 B All patients Arm A Arm B Events/patients 25/30 8/10 17/20 Median, months 5.8 7.2 4.8 C All patients Arm A Arm B Events/patients 27/30 8/10 19/20 Median, months 3.7 7.2 3.5 Figure S1. Kaplan-Meier – Overall patient survival (A) as of February 17th 2017, PFS by immune-related (B) and modified WHO (C) response criteria. Censored data are shown as open boxes on graph.

Figure S2. Evaluation of main immune cell population from samples collected before treatment (Pre). PBMC were drawn at 2 different time points before (pre; average of 2 values presented) during the course of the protocol. Main immune cell populations were evaluated by flow cytometry from these samples collected: T cells (CD3+), B cells (CD3-/CD14-/CD56-/CD19+), dendritic cells (CD3-CD19-CD14- HLA-DR+) myeloid cells (CD11c+), Natural Killers cells (CD3-CD19-CD14-CD56+CD16+). All error bars are standard error of the mean (SEM).

A B C D Figure S3. Evaluation of cell surface activation markers on CD4+ and CD8+ T lymphocyte subsets. Levels of CD25 on CD4+ naïve or effector T cells (A Tn: CD3+/CD4+/CD45RA+/CCR7+, Teff: CD3+/CD4+/CD45RA+/CCR7-) and CD69 on CD8+ naive or effector CD8+ T cells (B Tn: CD3+/CD8+/CD45RA+/CCR7+, Teff: CD3+/CD8+/CD45RA+/CCR7-) were evaluated from PBMCs during the treatment. C CD25+CD4+ effector T cells (Teff; CD4+/CD45RA+/CCR7-/CD62L-) levels in pre-samples. Each point represents a donor, average is outlined, and error bars represent SEM. *: p<0.05, **:p<0.01 from a one-way ANOVA with Bonferroni post hoc test. D Kaplan-Meier OS curves for CD25+CD4+ effector T cells population (stratified by mean level at baseline). P value was calculated using the log-rank test and is shown on the graph.

Figure S4. Bm classification of B cell subsets Figure S4. Bm classification of B cell subsets. Gating strategy for Bm1-Bm5 peripheral B cells (CD38 vs. sIgD, on CD3-/CD14-/CD56-/CD19+ cells).

A B CD279 (PD-1) on CD4+ T lymphocytes Treg in CD4+ T lymphocyte population Figure S5. T cell subsets (CD4+PD-1+ and Tregs) analysis throughout treatment. A CD279 (PD-1) levels from total CD4+ T lymphocytes evaluated by flow cytometry (CD3+/CD8-/CD4+/PD-1+; top panels). B regulatory T cells (Treg) labelled as CD4+/CD25hi/FoxP3+ staining of peripheral cells (top section). A and B Kaplan-Meier OS curves for patients with high or low proportions of CD4+PD-1+ T cells at week 10 (A; bottom panel) and of Tregs at baseline (B; bottom panel) levels. Cutoff thresholds for high a low levels were defined from the mean. P values were calculated using the log-rank test and are shown on each graph.

A CD278 (ICOS) on CD4+ and CD8+ T lymphocytes B Figure S6. ICOS expression on T cells throughout treatment. A ICOS expression on CD4+ (left) and CD8+ (right) peripheral T lymphocytes. All error bars are SEM. B Kaplan-Meier OS curves for ICOS levels at Week 10 (W10, cutoff defined from the mean) for CD4+ (left) and CD8+ (right). P values were calculated using the log-rank and are shown on each graph.