Inflammatory level under different p53 mutation status and the regulation role of curcumin in tumor microenvironment

• Published in: Immunobiology (1979) Vol. 227; no. 2; p. 152177
• Main Authors: Xu, Liping, Xie, Xiaoli, Li, Xinbo, Duan, Wenfang, Qiu, Lei, Liu, Huan, Luo, Ying
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier GmbH 01.03.2022
• Subjects: Carcinogenesis; Curcumin; Curcumin - pharmacology; Humans; Immune modulation; Inflammation - drug therapy; Inflammation - genetics; Mutation; Neoplasms - drug therapy; Neoplasms - genetics; Neoplasms - pathology; P53 mutation; Tumor associated macrophage; Tumor microenvironment; Tumor Microenvironment - genetics; Tumor Suppressor Protein p53 - genetics; MCP-1; TNFα; CSF1; DMSO; CXCR4; sIL-1Ra; MTT; LPS; NF-κB; DMEM; Arg-1; TAMs; Tumor associated macrophage; OD; FBS; RT-PCR; IC50; CCL3; iNOS; Curcumin; IACUC; Immune modulation; IFNγ; PBS; MEFs; Tumor microenvironment; PMA; Tregs; STAT3; DAB2IP; CM; TRAF2; OSMR; TME; MMP9; TCGA; PPARγ; ECL; SDS-PAGE; IL6; ROS; IRF5; GAPDH; P53 mutation; ERK
• ISSN: 0171-2985; 1878-3279
• DOI: 10.1016/j.imbio.2022.152177

•Inflammatory level was up-regulated under p53 mutation status in tumor environment.•p53 mutations educated M2 profile polarization of macrophages in tumor environment.•Curcumin reprogrammed p53 mutation educated M2 macrophages back towards M1 profile.•In vitro curcumin application significantly suppressed tumor growth in vivo. The inflammation is tightly associated with tumor development, promoting or inhibiting tumorigenesis. And mutant p53 is speculated to promote inflammation and tumorigenesis. The tumor associated macrophages are usually educated to present the anti-inflammatory profile to tune down antitumor immunity. However, the impact of p53 mutants on macrophages is not clear. Here, we compared the basal inflammatory level and macrophage profiles in tumor cells and tumor samples with different p53 mutations. Data revealed that a lower inflammatory level was maintained in immune organs and tumor cells with p53 point mutations than those with p53 null mutation. Using the tumor cell-derived conditional media to culture macrophages, we found that the media from cells with p53 mutations, especially the point mutations, could decrease M1 markers and inhibit phagocytosis, suggesting the p53 mutation promoted M2 profile polarization. To target the p53 mutation induced M2 macrophage polarization, we applied low-concentration curcumin to the tumor cells with different p53 mutations. The data showed that curcumin could inhibit STAT3 signal and decrease PPARγ and CSF1 in tumor cells and tumor samples. In vitro, the co-culture assays showed that the curcumin treatment shifted p53 mutation educated macrophages back towards M1 profile. In vivo, the curcumin-treated MEFs showed obvious tumor inhibition, and the tumor samples displayed inhibited M2 markers. Results suggested that curcumin could inhibit p53 mutation educated macrophage induction and suppress M2-promoted tumorigenesis. Our study illustrated the inflammatory level under different p53 status and the inflammatory regulated role of curcumin in tumor environment. This study might provide a potential method in tumor personalized treatment aiming immune therapy in different p53 status.