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. Author manuscript; available in PMC: 2023 Jan 6.
Published in final edited form as: Cancer Discov. 2022 Jul 6;12(7):1742–1759. doi: 10.1158/2159-8290.CD-21-0900

Figure 7. VitE enhances immune induction therapies to augment immunotherapy.

Figure 7.

A, Diagram of the experimental paradigm (top) and growth curves of orthotopic B16-GMCSF tumors (bottom) in mice vaccinated with or without GVAX (s.c. at day 1, 4, 7), then treated with vehicle or VitE (50mg/kg/day) by oral gavage from day 4 to day 20 (n=6/group).

B, Tumor weight of 4T1 tumors from mice treated with vehicle, GVAX, ICT (anti-PD1/anti-CTLA4), or GVAX+ICT in combination with vehicle or VitE (50mg/kg/day, oral gavage from day 4 to day 25). Tumors were harvested on day 25 post-inoculation.

C, Flow cytometric analysis (left) and quantification (right) of gp70 tetramer+ CD8+ T cells in 4T1 tumors collected at day 14 post-implantation from mice under indicated treatments (n=3–5/group).

D, Kaplan-Meier survival curve of 4T1 tumor-bearing mice treated with vehicle, low dose of Doxorubicin (Dox, 5mg/kg by i.v.), ICT (anti-PD1/anti-CTLA4), or Dox+ICT plus vehicle- or VitE-administrations (n=5–10).

E, Measurement of maximal tumor diameter in HY1936 KPC tumor-bearing mice treated with GEM (gemcitabine, 25 mg/kg, i.p.) and ICT (anti-PD1/anti-CTLA4) plus vehicle- or VitE-administrations (n=4–5).

F, Representative magnetic resonance images (MRI) of mice with established HY19636KPC PDAC tumors (yellow outline) after indicated treatments for 20 days.

G, Kaplan-Meier survival curve of HY19636KPC tumor-bearing mice treated with vehicle, GEM (gemcitabine, 25 mg/kg, i.p.), GEM + ICT (anti-PD1/anti-CTLA4) plus vehicle or VitE administrations.

H, Model of VitE reinvigorating TADCs function and boosting antitumor immunity. Dendritic cells (DCs) are central regulators of the cancer-immunity cycle. Upon VitE treatment, VitE reinvigorates dysfunctional TADCs by inhibiting pSHP1/SHP1 to enhance cross-presentation of DCs and DC-EVs, which synergize with ICT and/or DC-enrichment immune induction therapies leading to effective antitumor immunity.

Error bars, s.e.m. One-way ANOVA with Tukey’s multiple comparison post-test (A, B, C). Two-sided log-rank test (D, G). The statistical significance is defined by P-value: ns, no significant. *P < 0.05, ***P < 0.001, ****P < 0.0001.