Fig. 7: Neutralizing IL-17 promotes pro-inflammatory tumor immune microenvironment.

A Percent of CD45⁺CD3⁺ total CD8⁺ T cells and percentage of exhausted, memory/effector, and naive CD8⁺ T-cell subpopulations gated by the indicated markers from 344SQ tumors from the experiment in Fig. 6F. Data are presented as mean values ± SD. n = 4–5. Data were analyzed using unpaired Students’ t test. *P < 0.05; **P < 0.01. B Percent of CCR6⁺ and CCR5⁺RORγt⁺ Th17 cells gated from total CD4⁺ T-cell population. Data are presented as mean values ± SD. n = 4–5. Data were analyzed using unpaired Students’ t test. *P < 0.05; **P < 0.01. C Proposed working model of MEK inhibitor and anti-PD-L1 combinatorial drug resistance. Initial response to combination therapy promotes CD4⁺ T-cell differentiation into Th17 cells, which secrete IL-17 and IL-22 to promote resistance to MEK inhibition and PD-L1 blockade. Neutralization of IL-17 in combination with MEK inhibition and PD-L1 blockade abrogates resistant tumor outgrowth.