Fig. 6: Neutralizing IL-17 abrogates resistance to MEK inhibition and PD-L1 blockade combination therapy. | Nature Communications

Fig. 6: Neutralizing IL-17 abrogates resistance to MEK inhibition and PD-L1 blockade combination therapy.

From: Th17 cells contribute to combination MEK inhibitor and anti-PD-L1 therapy resistance in KRAS/p53 mutant lung cancers

Fig. 6

A In vivo tumor volume measurements at indicated time points for 344SQ subcutaneous tumors in syngeneic wild-type mice after daily treatments with 25 mg/kg AZD6244 in combination with weekly treatments with 200 µg PD-L1 and/or 200 µg IL-17 blocking antibody beginning at week 3 of tumor growth. Solvent + IgG (black), daily 25 mg/kg AZD6244 (blue), weekly treatment with 200 µg PD-L1 blocking antibody (green), weekly treatment with 200 µg IL-17 blocking antibody (grey), combination blocking antibodies 200 µg PD-L1 + 200 µg IL17 (purple), combination 25 mg/kg AZD6244 + weekly 200 µg blocking antibody IL17 (pink), combination 25 mg/kg AZD6244 + weekly 200 µg blocking antibody PD-L1 (red), triple combination 25 mg/kg AZD6244 + weekly 200 µg blocking antibody PD-L1 + 200 µg blocking antibody IL17 (teal). Data are presented as mean values ± SD. n = 4–5. Data were analyzed using unpaired Students’ t test. *P < 0.05. B, C Tumor weights B and lung metastatic nodules C of 344SQ tumors at endpoint of experiment in A. Data are presented as mean values ± SD. n = 4–5. Data were analyzed using unpaired Students’ t test. *P < 0.05; **P < 0.01. D In vivo tumor volume measurements at indicated time points for 393P-AR1 subcutaneous tumors in syngeneic WT mice after daily treatments with 25 mg/kg AZD6244 in combination with weekly treatments with 200 µg PD-L1 and/or 200 µg IL-17 blocking antibody beginning at day 12 of tumor growth. Solvent + IgG (black), daily 25 mg/kg AZD6244 (blue), weekly treatment with 200 µg PD-L1 blocking antibody (green), weekly treatment with 200 µg IL-17 blocking antibody (grey), combination blocking antibodies 200 µg PD-L1 + 200 µg IL17 (purple), combination 25 mg/kg AZD6244 + weekly 200 µg blocking antibody IL17 (pink), combination 25 mg/kg AZD6244 + weekly 200 µg blocking antibody PD-L1 (red), triple combination 25 mg/kg AZD6244 + weekly 200 µg blocking antibody PD-L1 + 200 µg blocking antibody IL17 (teal). Data are presented as mean values ± SD. n = 4–5 mice per group. Data were analyzed using unpaired Students’ t test. **P < 0.01. E Tumor weights of 393P-AR1 tumors at endpoint of experiment after indicated treatment combinations from D. Data are presented as mean values ± SD. n = 5. Data were analyzed using unpaired Students’ t test. *P < 0.05; ***P < 0.001. F In vivo tumor volume measurements at indicated time points for 344SQ subcutaneous tumors in syngeneic wild-type mice after daily treatments with 25 mg/kg AZD6244 in combination with weekly treatments with 200 µg PD-L1 blocking antibody or 200 µg IL-17A blocking antibody. Black arrow indicates treatment start time. Solvent + IgG (black), combination 25 mg/kg AZD6244 + weekly 200 µg blocking antibody PD-L1 (red), triple combination 25 mg/kg AZD6244 + weekly 200 µg blocking antibody PD-L1 + 200 µg blocking antibody IL17 (teal). Data are presented as mean values ±SD. n = 9 mice per group. Data were analyzed using unpaired Students’ t test. *P < 0.05; **P < 0.01; ***P < 0.001. G, H Tumor weights G and lung metastatic nodules H of 344SQ tumors at endpoint of experiment in F. Data are presented as mean values ± SD. n = 9 mice per group. Data were analyzed using unpaired Students’ t test. *P < 0.05; *P < 0.01; ***P < 0.001.

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