American Society of Hematology

Figure 4.

$Figure 4. Immunotherapy with anti-PD-1 enhances anti-CD20 efficacy in the aggressive immunocompetent ABC-DLBCL mouse model. (A) Overall survival of murine ABC-DLBCL pBIC mice treated with different immunotherapy combinations. (B) Relative changes in splenic transversal areas measured by ventral ultrasound of pBIC mice (>180 days, with evidence of splenomegaly, n = 3) at 4 sequential times during immunotherapy treatment, as indicated in the scheme at the top. Representative ultrasound sections of the spleen are shown on the right. Scale bars, 1 mm. (C) Representative immunohistochemical staining of GFP, CD4, and CD8 to label T-cell infiltration in murine pBIC lymphomas (>180 days) that had received 4 weeks of immunotherapy. Scale bars, 200 μm. (D) Comparative percentages of splenic B220+GFP+ lymphoma cells from pBIC lymphomas (>180 days) in response to different 4-week immunotherapy regimens (n3). (E) Pie charts showing percentages of immune cells in the spleen pBIC mice (>180 days) after 4-week immunotherapy (n = 3). (F) Comparative fractions of PD-1-positive T cells in the TME of pBIC mice (>180 days) after 4-week immunotherapy (n = 3). (G) Heat maps of mean expression intensity of coinhibitory/exhaustion (top) and activation/differentiation (bottom) surface markers within lymphocyte subsets detected by RPhenograph clustering (n = 3 mice × 4 groups). Distribution of these cell populations in response to 4-week immunotherapy (n = 3) is represented in t-SNE maps and colored. Percentages indicate average abundance of each cell population in the corresponding treatment group. (H) Comparative fractions of PD-L1-positive or PD-L1-negative cells within the compartment of lymphoma cells (CD19+GFP+) or neighbor normal B cells (CD19+GFP−) from pBIC mice (>180 days) after 4-week immunotherapy (n = 3). (I) FACS analysis to assess the specific depletion of lymphoma or normal B cells in the spleen of pBIC mice (>180 days) after 4-week immunotherapy (n = 3). (J) Percentages of reappearing splenic lymphoma cells (CD20+GFP+) or neighbor normal B cells (CD20+GFP−) during a resting period of 8 weeks after anti-CD20–based immunotherapy that can efficiently deplete the B-cell compartment in pBIC mice (>180 days, n3). MS, median survival; UNT, untreated.$

Immunotherapy with anti-PD-1 enhances anti-CD20 efficacy in the aggressive immunocompetent ABC-DLBCL mouse model. (A) Overall survival of murine ABC-DLBCL pBIC mice treated with different immunotherapy combinations. (B) Relative changes in splenic transversal areas measured by ventral ultrasound of pBIC mice (>180 days, with evidence of splenomegaly, n = 3) at 4 sequential times during immunotherapy treatment, as indicated in the scheme at the top. Representative ultrasound sections of the spleen are shown on the right. Scale bars, 1 mm. (C) Representative immunohistochemical staining of GFP, CD4, and CD8 to label T-cell infiltration in murine pBIC lymphomas (>180 days) that had received 4 weeks of immunotherapy. Scale bars, 200 μm. (D) Comparative percentages of splenic B220⁺GFP⁺ lymphoma cells from pBIC lymphomas (>180 days) in response to different 4-week immunotherapy regimens (n3). (E) Pie charts showing percentages of immune cells in the spleen pBIC mice (>180 days) after 4-week immunotherapy (n = 3). (F) Comparative fractions of PD-1-positive T cells in the TME of pBIC mice (>180 days) after 4-week immunotherapy (n = 3). (G) Heat maps of mean expression intensity of coinhibitory/exhaustion (top) and activation/differentiation (bottom) surface markers within lymphocyte subsets detected by RPhenograph clustering (n = 3 mice × 4 groups). Distribution of these cell populations in response to 4-week immunotherapy (n = 3) is represented in t-SNE maps and colored. Percentages indicate average abundance of each cell population in the corresponding treatment group. (H) Comparative fractions of PD-L1-positive or PD-L1-negative cells within the compartment of lymphoma cells (CD19⁺GFP⁺) or neighbor normal B cells (CD19⁺GFP⁻) from pBIC mice (>180 days) after 4-week immunotherapy (n = 3). (I) FACS analysis to assess the specific depletion of lymphoma or normal B cells in the spleen of pBIC mice (>180 days) after 4-week immunotherapy (n = 3). (J) Percentages of reappearing splenic lymphoma cells (CD20⁺GFP⁺) or neighbor normal B cells (CD20⁺GFP⁻) during a resting period of 8 weeks after anti-CD20–based immunotherapy that can efficiently deplete the B-cell compartment in pBIC mice (>180 days, n3). MS, median survival; UNT, untreated.

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