Figure 1. Dietary VitE augments ICT efficacy dependent on DCs.
A, Overall survival of melanoma patients who took dietary vitamin E supplement (VitE, n=133) during ICT treatment (Anti-PD-1/PDL1) compared with patients who didn’t take VitE and/or multivitamins (No VitE, n=2,266).
B, Overall survival of a mixed cohort of cancer patients (599 breast cancer, 914 colon cancer, and 990 kidney cancer) who took dietary vitamin E supplement (VitE, n=127) during ICT treatment compared with patients who didn’t take VitE and/or multivitamins (No VitE, n=2, 376).
C, Growth curve of EMT6 mammary tumors in mammary fat pads of BALB/c mice treated with vehicle, VitE (50mg/kg, oral gavage), ICT (anti-PD1, 200 mg/mouse, by i.p.) or VitE+ICT.
D-F, Growth curves of orthotopic B16-GMCSF (D, left), B16-F10 (E), B16-FLT3L (F) melanomas in C57BL/6 mice treated with vehicle, VitE (50mg/kg, oral gavage), ICT (anti-PD1, 200μg/mouse and anti-CTLA4, 100μg/mouse by i.p.), or VitE+ICT. Flow cytometry quantification of GranzymeB+CD8+ tumor-infiltrating lymphocytes (TILs) in B16-GMCSF tumor tissues collected 20 days post-implantation (D, right). (n=5/group).
G, Growth curves (left) and Kaplan–Meier survival curves (right) of C57BL/6 mice bearing B16-GMCSF melanomas treated with vehicle (n=4), Cyt c that depletes DCs (n=5), ICT (anti-PD1/anti-CTLA4) +VitE (n=8), or ICT+VitE+Cyt c (n=10).
Mean ± s.e.m (C, D, E, F, G). One-way analysis of variance (ANOVA) and Tukey’s test for multiple comparisons (C, D, E, F, G tumor growth), log-rank (Mantel-Cox) test survival comparison (A, B, G). The statistical significance is defined by P-value: ns, no significant. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.