Regulatory T cells, interleukin (IL)‐6, IL‐8, Vascular endothelial growth factor (VEGF), CXCL10, CXCL11, epidermal growth factor (EGF) and hepatocyte growth factor (HGF) as surrogate markers of host immunity in patients with renal cell carcinoma

Abstract

Objective To identify a phenotype that could be informative and prognostic in patients with renal cell carcinoma (RCC) peripheral blood was evaluated for TH1, TH2, regulatory T cells (Tregs), natural killer (NK) and NKT cells and for cytokines/chemokines. Patients and Methods Peripheral blood from 77 patients with RCC and 40 healthy controls was evaluated by flow cytometry using monoclonal antibodies against CD4, CD25, FoxP3, CD45RA, CD45RO, CD152, CD184, CD279, CD3, CD16, CD56, CD161, CD158a, CD4, CD26, CD30, CD183 and CD184. A concomitant evaluation of 38 molecules was conducted in patients’ serum using a multiplex biometric ELISA‐based immunoassay. Results The number of NK cells CD3−/CD16+, CD3−/CD16+/CD161+ (NK) and CD3−/CD16+/CD161+/CD158a+ (NK‐ Kir 2+) was greater in the patients with RCC (P < 0.05); and the number of Treg cells CD4+/CD25high+/FOXP3+ and the subset CD4+/CD25high+/FOXP3+/CD45RA+ (naïve) and CD45R0+(memory) cells, were greater in the patients with RCC (P < 0.001). An increase in the following was observed in the serum of patients with RCC compared with healthy controls: interleukin (IL)‐4, IL‐6, IL‐8, IL‐10, G‐CSF, CXCL10, CXCL11, hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF). According to Ingenuity Pathway Analysis (IPA), CXCL10, IL‐6, IL‐8, epidermal growth factor (EGF), HGF and VEGF were associated with a network that controls cellular movement, tissue development and cellular growth. Kaplan–Meier analysis for disease‐free survival showed that high numbers of CD4+/CD25high+/FOXP3+/CD45RA+ (Treg naïve) and low numbers of CD3−/CD16+/CD161+/CD158a+ (NK‐Kir+) cells predict short disease‐free survival in patients with RCC. Conclusion Concomitant evaluation of Treg (CD4+/CD25high+/FOXP3+ and CD4+/CD25high+/FOXP3+/CD45RA+) and of six soluble factors (IL‐6, IL‐8 ,VEGF, CXCL10, CXCL11, EGF, HGF) might be a surrogate marker of host immunity in patients with RCC.

Immune Contexture, Immunoscore, and Malignant Cell Molecular Subgroups for Prognostic and Theranostic Classifications of Cancers

“…In addition to express several TAM-attracting molecules, RCC tumor cells secret chemokines that recruit T lymphocytes, including CCL4, CCL5, CXCL9-11, and CXCL16 (Oldham et al, 2012;Polimeno et al, 2013; Figure 4 DC compartmentalization and prognosis in RCC. Cartoon depiction of the two major types of DCs in ccRCC.…”

Interleukin-6 as an emerging regulator of renal cell cancer

“…IL-6 is secreted by many renal cancer cell lines and is abundant in the serum of 50% of the patients with metastatic [39,40] renal cell cancer [39][40][41][42]. Moreover, it has been demonstrated that primary RCC cultures secrete elevated levels of IL-6 [43].…”

“…Ingenuity pathway analysis showed that 6 molecules are involved in cancer and inflammatory response; EGF, HGF, IL-6, IL-8, and vascular endothelial growth factor (VEGF) are implicated in renal and urological disorders; and CXCL10, EGF, HGF, and IL-6 are implicated in the proliferation of renal cells [42]. IL-6 was also shown to act as an intracrine growth factor through an intracrine loop in RCC cell lines [44].…”

Identification of biomarkers for ischemic cardiomyopathy based on microarray data analysis

“…CXCL10 is suggested to be the master regulator of myocardial inflammatory cell migration, and may contribute to the clinical progression to life-threatening cardiomyopathy [33]. Previous studies have demonstrated that some factors such as CXL10 are associated with immunity in the process of disease [34,35]. The marked up-regulation of CXC chemokines (such as CXCL10) is the early event in ICM development [36].…”