Maraba treatment sensitizes 4T1 tumors to immune checkpoint blockade

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Nat. Rev. Clin. Oncol. doi: /nrclinonc

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Molecular Therapy - Oncolytics

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PD and efficacy of AZD4785 in a KRAS wild-type lung cancer PDX model

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Fig. 6 Maraba treatment sensitizes 4T1 tumors to immune checkpoint blockade. Maraba treatment sensitizes 4T1 tumors to immune checkpoint blockade. (A) Cell surface programmed death ligand 1 (PD-L1) expression on 4T1, EMT6, and E0771 cells after an incubation with Maraba-infected 4T1 cell–conditioned medium with or without IFN-αR1–blocking antibody. MFV, mean fluorescence value; MRB, Maraba. (B) Mice with 4T1 tumors were treated intratumorally with Maraba (days 7 to 11) and sacrificed on day 20. The graph shows the percentage of T cells that were FOXP3+. Two-tailed unpaired t test, **P < 0.01. (C) Mice bearing 4T1 tumors were treated intratumorally with Maraba (days 7 to 11) followed by anti-cytotoxic T lymphocyte–associated protein 4 (CTLA4) and anti–PD-1 (programmed cell death protein 1) antibodies injected intraperitoneally on days 21, 23, 25, 27, and 29. The tumors were measured on day 31 (three separate experiments). The graph shows the volume of each tumor relative to the average volume of the tumors from the control group. Unpaired two-tailed t test, *P < 0.05, **P < 0.01, ***P < 0.001. ICI, immune checkpoint inhibitor. (D) Treatment schedule used in (E), (F), and (G). (E to G) Tumor growth and Kaplan-Meier survival analysis of 4T1 (E), EMT6 (F), or E0771 (G) tumor-bearing mice using the tumor rechallenge model. The dotted lines indicate the days of Maraba treatment. Unpaired multiple two-tailed t test, *, #, xP < 0.05, **,xxP < 0.01, ***,xxxP < 0.001. The symbol “*” denotes the difference between NT and Maraba + ICI. The symbol “#” denotes the difference between Maraba and Maraba + ICI. The symbol “x” denotes the difference between ICI and Maraba + ICI. For survival curves, **P < 0.01, ***P < 0.001 (Mantel-Cox test). Marie-Claude Bourgeois-Daigneault et al., Sci Transl Med 2018;10:eaao1641 Published by AAAS