Higher Serum C-reactive Protein Level Represents the Immunosuppressive Tumor Microenvironment in Patients With Clear Cell Renal Cell Carcinoma

• Published in: Clinical genitourinary cancer 2018-12, Vol.16 (6), p.e1151-e1158
• Main Authors: Nakayama, Takayuki, Saito, Kazutaka, Kumagai, Jiro, Nakajima, Yutaka, Kijima, Toshiki, Yoshida, Soichiro, Kihara, Kazunori, Fujii, Yasuhisa
• Format: Article
• Language: English
• Subjects: C-reactive protein; Immune suppression; Prognosis; Renal cell carcinoma; Systemic inflammation
• ISSN: 1558-7673; 1938-0682
• DOI: 10.1016/j.clgc.2018.07.027

C-reactive protein (CRP), a representative inflammatory marker, could serve as a biomarker in renal cell carcinoma because CRP is an important prognostic factor. However, its detailed mechanism remains unknown. This study showed that higher CRP levels correlated with the tumor immune microenvironment, which leads to a worse prognosis. These findings can help to clarify the underlying mechanisms between the presence of systemic inflammatory reaction and prognosis. The aim of this study is to investigate the association between tumor immune microenvironment and CRP in patients with renal cell carcinoma (RCC) to explore the underlying mechanisms between CRP level and prognosis. Immunohistochemical measurement of CD4, CD8, CD163 (M2 macrophages), and Foxp3 (Regulatory T [Treg] cells) was performed in patients with clear-cell RCC (n = 111) treated with radical or partial nephrectomy at our institution. The association between immunohistochemical status and preoperative serum CRP level and cancer-specific survival (CSS) was analyzed. Thirty-three patients (30%) had a high CRP level (≥ 5.0 mg/L), and the CSS rate was significantly worse among these patients than among the remaining patients (P < .001). In patients with strong infiltration of CD8+, Foxp3+, or CD163+ cells, CRP levels were significantly higher (P = .041, P = .001, and P = .035, respectively), and CSS was significantly worse compared with patients with weak infiltration (P = .040, P = .026, and P < .001, respectively). In multivariate analysis, strong CD163+ cells infiltration (P = .001) as well as pathologic T3 (P = .036), lymph-node involvement (P = .007), distant metastasis (P < .001), and Fuhrman nuclear grade 4 (P = .003) were independent prognostic factors for CSS. Infiltration of the immunosuppressive cells known as Tregs and M2 macrophages in the tumor microenvironment is associated with higher CRP and poor prognosis in patients with clear-cell RCC. CRP could reflect an immunosuppressive microenvironment. This study was designed to assess the association between serum C-reactive protein level and tumor immune microenvironment derived from immunohistochemical staining for CD4, CD8, CD163 (M2 macrophages), and Foxp3 (regulatory T cells) in 111 patients with clear-cell renal cell carcinoma. The results indicated serum C-reactive protein level reflects the immunosuppressive tumor microenvironment in patients with clear-cell renal cell carcinoma.