Fig. 4 Rational therapeutic modulation of the tumor microenvironment sensitizes tumors to ICB. Rational therapeutic modulation of the tumor microenvironment.

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Fig. 4 Rational therapeutic modulation of the tumor microenvironment sensitizes tumors to ICB. Rational therapeutic modulation of the tumor microenvironment sensitizes tumors to ICB. (A) URA predicted regulators of the response-associated gene signature in mouse models (red, positive correlation; blue, negative correlation). (B) URA-predicted regulators in responders versus nonresponders of the patient cohort (n = 192) (23). (C) Sensitizing treatment schedule. (D to G) Survival curves of Renca (D), AB1 (E), AE17 (F), and B16 tumor–bearing mice (G) mice treated with the triple combination [poly(I:C) + IFNγ + anti–IL-10], followed by ICB compared to ICB alone (n = 10 per group; n = 15 for AE17). (H) Survival curves of Renca tumor–bearing mice treated with single agent therapy [anti–IL-10, poly(I:C), or IFNγ] versus the triple combination before ICB. (I) Survival curves of Renca-bearing mice treated with double-agent therapy versus the triple combination before ICB (n = 10 mice per group, two independent experiments of five mice per group; log-rank test compared to ICB-only group, *P < 0.05, **P < 0.01, ***P < 0.001). (J) Treatment schedule to test ICB followed by triple-combination therapy. (K) Survival curves of Renca-bearing mice treated with the triple combination followed by ICB, as shown in (C), or with the reverse schedule, as shown in (J) (n = 10 mice per group, two independent experiments of five mice per group; log-rank test. *P < 0.05, **P < 0.01). Rachael M. Zemek et al., Sci Transl Med 2019;11:eaav7816 Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works