Introduction

C-reactive protein (CRP), a representative inflammatory marker, has been shown to be a prognostic biomarker for renal cell carcinoma (RCC) (Saito K et al. Nat Rev Urol. 2011). Recently, several studies have reported that the invasion of immunosuppressive regulatory T cells (Treg) and M2 macrophages correlates with poor clinical prognosis in various cancers. In this study, we investigated the association between tumor immune microenvironment including invasions of Treg and M2 macrophages and CRP in RCC patients to explore the mechanisms underlying the association between CRP level and prognosis.

Methods

Immunohistochemical (IHC) measurement of CD4, CD8, CD163 (M2 macrophages), and FOXP3 (Treg) was performed in clear-cell RCC (ccRCC) patients (n =111) treated with radical or partial nephrectomy. CD4+, CD8+, and CD163+ cells were counted and the optimal cut-off scores for CD4, CD8 and CD163 were determined through receiver-operating characteristic (ROC) analysis. Patients were classified into groups according to FOXP3 positive or negative status. The association between IHC status and preoperative serum CRP level and cancer-specific survival (CSS) was analyzed.

Results

Median follow-up period was 8.5 years. pT stage was pT1 in 58%, pT2 in 5%, pT3 in 35% and pT4 in 2% of patients. Lymph node involvement and distant metastasis were seen in 4% and 20% of patients, respectively. 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 <0.0001). In patients with strong invasion of CD8+, CD163+ or FOXP3+ cells, CRP levels were significantly higher (Figure 1) and CSS was significantly worse (Figure 2) compared to patients with weak invasion.

Conclusions

Invasion of the immunosuppressive cells known as Tregs and M2 macrophages in the tumor microenvironment is associated with higher CRP and poor prognosis in ccRCC patients. CRP indicates an immunosuppressive microenvironment.

Funding

none