Abstract 1538: Impact of C-reactive protein on the efficacy of immune checkpoint inhibitors in non-small cell lung cancer

Abstract Background: Immune checkpoint inhibitors (ICIs) therapy has achieved remarkable success in the treatment of non-small cell lung cancer (NSCLC). Clinical studies have suggested a correlation between C-reactive protein (CRP) levels and treatment efficacy, but it remains unclear whether CRP can directly impact the efficacy. Therefore, we investigated the imapct of CRP on the efficacy of ICIs in NSCLC. Methods: The tumor growth model was established in CRP knockout and wildtype mice by injecting LLC cells to evaluate the effect of CRP on tumor proliferation. The frequencies and phenotypes of macrophages and T cells in mouse tumors were detected by flow cytometry. The impact of CRP on macrophage polarization was evaluated using flow cytometry and IF, while its impact on T cell chemokines CCL5, CXCL9, and CXCL10 was analyzed by ELISA and qRT-PCR. mCRP and α-PD-1 were implemented in C57/BL6 mice injected with LLC cells to evaluate the effect of mCRP on tumor immunotherapy. The frequencies of T cells in mouse tumors were detected by flow cytometry. Expression of mCRP and infiltration of immune cells in human NSCLC tissues were analyzed using IHC. Results: We found that tumor progression was enhanced and the proportion of tumor-infiltrated M1 macrophages was decreased in CRP knockout mice. Using human PBMC-derived macrophage and RAW264.7 cell lines, we demonstrated that the monomeric form of CRP, known as mCRP, induced M1 polarization of macrophages, leading to increased secretion of CCL5, CXCL9, and CXCL10. In tumor bearing mice, mCRP treatment enhanced anti-tumor immunity and suppressed tumor progression by increasing CD4+ and CD8+ T cell recruitment. Surprisingly, the combined treatment of mCRP and α-PD-1 induced more significant tumor regression than α-PD-1 treatment alone. Additionally, high level of mCRP in NSCLC tissues is correlated with a more inflamed tumor microenvironment phenotype. Conclusion: mCRP can enhance the efficacy of immune checkpoint inhibitors in NSCLC by activating anti-tumor immunity. Citation Format: Wenyuan Li, Hui Guo. Impact of C-reactive protein on the efficacy of immune checkpoint inhibitors in non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1538.