Triggering PD-1 in B cells suppresses tumor-specific immunity and promotes disease progression. Triggering PD-1 in B cells suppresses tumor-specific immunity.

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Triggering PD-1 in B cells suppresses tumor-specific immunity and promotes disease progression. Triggering PD-1 in B cells suppresses tumor-specific immunity and promotes disease progression. A, physical contact between CD8+ T cells (red) and CD79a+ B cells (green) in HCC peritumoral stroma (N = 8). Scale bar, 50 μm. B and C, FACS-sorted PD-1− effector T cells from tumor were left untreated or were incubated for 24 hours with FACS-sorted autologous tumor B cells (5:1) supplemented with 25 μg/mL tumor mass lysate in the absence or presence of 10 μg/mL anti–PD-1 or anti–IL10-receptor (IL10R) antibody. Production of IFNγ was determined by ELISpot (B). Production of granzyme B and perforin was detected by FACS (C). Data represent mean ± SEM of four independent experiments (N = 4 for B; N = 5 for C). *, P < 0.05; **, P < 0.01; ***, P < 0.001 (Student t test). D, FACS-sorted PD-1−CD8+ T cells alone or together with enriched PD-1hi B cells derived from C57BL/10J Hepa1-6 hepatoma were added in the culture of Hepa1-6 cells (10:1) in the presence or absence of mitomycin C–treated mouse PD-L1–expressing HEK293T cells, supplemented with rat IgG or blocking antibody against PD-1 or IL10R (5 μg/mL). T-cell cytotoxicity was detected by FACS. Results represent four independent experiments. E–I, Hepa1-6 hepatoma-bearing C57BL/10 recipient mice received adoptive transfer of sorted B cells pooled from tumors of donor mice along with injection of antibody as described in Methods. Tumor volumes (E and F) and immunohistochemical detection of CD8 infiltration in these tumors (G and H) as well as CD8 function detected by FACS (I) are shown. Scale bar, 100 μm. Results represent mean ± SEM of four independent experiments (N = 11 for F; N = 8 for H; N = 3 for I). #, P < 0.05; ##, P < 0.01; ###, P < 0.001, compared with groups injected with IgG and transferred with PBS, or PD-1−/dim B cells, or PD-1hi B cells pretreated with PD-1–blocking antibody; *, P < 0.01; **, P < 0.001, compared with groups transferred with PD-1hi B cells and injected with anti–PD-L1 or anti-IL10R antibody (Student t test). Xiao Xiao et al. Cancer Discov 2016;6:546-559 ©2016 by American Association for Cancer Research