Concomitant NAFLD Facilitates Liver Metastases and PD-1-Refractory by Recruiting MDSCs via CXCL5/CXCR2 in Colorectal Cancer.

The infiltration level of CD8 + lymphocytes was significantly higher in the dual therapy group than those in other 3 groups (dual therapy vs control, 12.88% ± 7.89% vs 1.36% ± 0.93%, P = .008; dual therapy vs PD-1, 12.88% ± 7.89% vs 1.90% ± 1.03%, P = .010; dual therapy vs Reparixin, 12.88% ± 7.89% vs 3.01% ± 0.87%, P = .017) ( Figure 12 J ) The infiltration of CD8 + /PD-L1 + cytotoxic lymphocytes was also higher in the dual therapy group but just reached borderline significance (dual therapy vs control, 8.43% ± 8.68% vs 0.90% ± 0.90%, P = .071; dual therapy vs PD-1, 8.43% ± 8.68% vs 1.46% ± 0.84%, P = .090; dual therapy vs Reparixin, 8.43% ± 8.68% vs 2.39% ± 1.20%, P = .133) ( Figure 11 D ).

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The NAFLD background accelerated the growth of liver metastatic foci, and in mice without NAFLD background, Reparixin decreased the relative liver weight (CRLM + Reparixin vs CRLM, P = .067) and liver/body weight ratio (CRLM + Reparixin vs CRLM, P = .063) but did not reach statistical significance.

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