In patients with renal cell carcinoma, high levels of the inflammation marker C-reactive protein may signal the presence of an immunosuppressive tumor microenvironment, a feature associated with poor prognosis, investigators contend.
Among 111 patients with renal cell carcinoma (RCC) treated with either partial or radical nephrectomy, those with high C-reactive protein (CRP) levels had significantly worse cancer-specific survival (CSS) compared with patients with normal CRP levels, and CRP levels were significantly higher among patients whose tumors showed strong infiltration of immune-suppressor cells, reported Takayuki Nakayama, MD, of Tokyo Medical and Dental Graduate University in Japan, and his colleagues.
“We have found that CRP level is positively associated with the infiltration of Treg and M2 macrophage[s] in patients with RCC, indicating that CRP reflects an immunosuppressive microenvironment. However, further studies are required to confirm these findings and provide a better understanding of the association between host systemic inflammation and the immunosuppressive microenvironment,” they wrote in.
The investigators had previously proposed CRP as a biomarker for urologic malignancies, including RCC. The current study was designed to look at the association between CRP and the tumor microenvironment, and to determine whether serum CRP levels correlate with prognosis.
To do this, they performed immunohistochemistry studies of immune cells, including immunosuppressive M2 macrophages (CD4, CD8, and CD163 cells) and Foxp4 regulatory T cells (Tregs) on resected renal tissues from 111 patients with RCC treated in their center.
They found that 33 of the 111 patients (30%) had high CRP levels, defined as 0.5 mg/L or greater. These patients had a 5-year CSS rate of 51%, compared with 91% for patients with CRP levels below the 0.5 mg/L cutoff (P less than .001).
They also found that tumors with strong infiltration of M2 macrophages had significantly worse disease and poorer prognoses. For example, patients with strong infiltration of CD163-positive cells had higher tumor and nodal stages, as well as higher rates of distant metastases and higher Fuhrman nuclear grade (respective P values less than .001, = .003, less than .001, and = .008).
CRP levels were significantly higher among patients with strong infiltration of CD8-positive cells (P = .041), Foxp3-positive cells (P = .001), or CD163-positive (P = .035). These patients also had significantly worse CSS compared with patients with weak tumor infiltration of the respective cells (P = .040, P = .026, and P less than .001, respectively).
Independent prognostic factors for CSS in multivariate analysis included strong CD163-positive cell infiltration (P =.001), pathologic stage T3 (P = .036), lymph-node involvement (P = .007), distant metastasis (P less than .001), and Fuhrman nuclear grade 4 (P = .003).
The authors acknowledged that the study was limited by its retrospective design, small sample size, and limited analysis of components of the tumor microenvironment.
The study was supported by the Japan Society for the Promotion of Science. The authors reported having no conflicts of interest to disclose.
SOURCE: Nakayama T et al. Clin Genitourin Cancer. 2018 Aug 11. doi: 10.1016/j.clgc.2018.07.027.