AUTHOR=Wang Yongchun , Li Zhixiong , Huang Zhijie , Yu Xingjuan , Zheng Limin , Xu Jing 

TITLE=C-Reactive Protein Is an Indicator of the Immunosuppressive Microenvironment Fostered by Myeloid Cells in Hepatocellular Carcinoma

JOURNAL=Frontiers in Oncology

VOLUME=11

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.774823

DOI=10.3389/fonc.2021.774823

ISSN=2234-943X

ABSTRACT=<sec><title>Background</title><p>C-reactive protein (CRP) is a widely used marker of systemic inflammation and predicts poor clinical outcomes in patients with hepatocellular carcinoma (HCC); however, its significance in the local immune response at the tumor site is not clear.</p></sec><sec><title>Methods</title><p>Serum CRP levels of 329 HCC patients were detected before resection. Paired paraffin-embedded tumor samples were used to quantify immune cell populations, such as CD11b<sup>+</sup> myeloid cells, CD68<sup>+</sup> macrophages (Mφs), CD15<sup>+</sup> neutrophils, CD8<sup>+</sup> T cells, and CD206<sup>+</sup>, CD204<sup>+</sup>, CD163<sup>+</sup> and CD169<sup>+</sup> Mφs, by immunohistochemistry. Enrichment scores for 34 types of immune cells based on transcriptome data from 24 HCC samples were calculated by xCell. Overall survival of patients was analyzed using the Kaplan-Meier method.</p></sec><sec><title>Results</title><p>Serum CRP levels were correlated with liver functions and tumor stages in patients with HCC. The densities of CD68<sup>+</sup> tumor-associated macrophages (TAMs) and CD15<sup>+</sup> tumor-associated neutrophils (TANs) were significantly higher in patients with elevated serum CRP levels than in those with low CRP levels (both <italic>p &lt;</italic> 0.0001). Further analysis of TAM subtypes revealed that serum CRP levels were associated with CD204<sup>+</sup> and CD163<sup>+</sup> Mφ densities (<italic>p</italic> &lt; 0.0001 and <italic>p</italic> = 0.0003, respectively). Moreover, transcriptome data showed that CRP expression was associated with the expression of myeloid cell infiltration-related genes in HCC tumors. The combination of serum CRP with TAMs or TANs in both the nontumor and intratumor regions could represent a powerful criterion for predicting patient prognoses.</p></sec><sec><title>Conclusion</title><p>Serum CRP could serve as an indicator of an immunosuppressive TME in HCC, which could be of potential clinical application for treatment strategies targeting the TME.</p></sec>