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. Author manuscript; available in PMC: 2023 Apr 5.
Published in final edited form as: Nature. 2022 Oct 5;610(7931):373–380. doi: 10.1038/s41586-022-05254-3

Fig. 3 |. IL-35 ablation in B cells synergizes with STING agonist to modulate NK cell activity.

Fig. 3 |

a, Workflow of the pancreatic tumor modeling and treatment. B(Ebi3−/−) mice and B(Ebi3+/−) mice were orthotopically injected with KPC4662 or KPC2173 tumor cells and given cGAMP. b, Bone marrow reconstituted chimeric mice with B cell-specific deficiency in Il10 or p35 were orthotopically injected with KPC4662 tumor cells and treated with cGAMP (i.v.) every three days beginning on d8, with tumors harvested on d21. c, Weights of KPC4662 tumors from cGAMP− and PBS-treated B(Ebi3+/−) and B(Ebi3−/−) mice (left) and B(WT), B(Il10−/−) and B(p35−/−) chimeric mice (right) harvested on d21 (n=11 for Ctrl B(Ebi3+/−) and Ctrl B(Ebi3−/−), n=12 for cGAMP-treated B(Ebi3+/−) and cGAMP-treated B(Ebi3−/−), n=12 for Ctrl and cGAMP-treated B(WT), n=13 for Ctrl and cGAMP-treated B(Il10−/−), n=13 for Ctrl and cGAMP-treated B(p35−/−)). d, Tumor weights of cGAMP− or PBS-treated B(Ebi3+/−) and B(Ebi3−/−) mice bearing KPC2173 tumor on d21 (n=6 Ctrl B(Ebi3+/−), Ctrl B(Ebi3−/−) and cGAMP-treated B(Ebi3+/−); n=7, cGAMP-treated B(Ebi3−/−)). e, Frequency of tumoral CD19+IL-35+ B cells from (c). f, Frequency of tumoral CD45+CD8+ T cells from (c). g, Frequency of tumoral CD8+ T cells expressing GzmB from (c). h, Frequency of tumoral TNF+CD8+ T cells from (c). i, Frequency of tumoral CD45+NK1.1+ cells from (c). j, Frequency of tumoral CD45+NK1.1+ cells from (d). k, Frequency of NK1.1+ cells expressing GzmB from (c). Data represent a combination of three independent experiments for all panels except for (d, j – two experiments), with each symbol representing an individual animal and mean ± s.e.m. Statistical significance was determined by unpaired two-tailed Student’s t tests. P values indicated; NS, not significant.