Immune signature of tumor infiltrating immune cells in renal cancer

Oncoimmunology. 2015 Feb 3;4(1):e985082. doi: 10.4161/2162402X.2014.985082. eCollection 2015 Jan.


Tumor-associated immune cells have been discussed as an essential factor for the prediction of the outcome of tumor patients. Lymphocyte-specific genes are associated with a favorable prognosis in colorectal cancer but with poor survival in renal cell carcinoma (RCC). Flow cytometric analyses combined with immunohistochemistry were performed to study the phenotypic profiles of tumor infiltrating lymphocytes (TIL) and the frequency of T cells and macrophages in RCC lesions. Data were correlated with clinicopathological parameters and survival of patients. Comparing oncocytoma and clear cell (cc)RCC, T cell numbers as well as activation-associated T cell markers were higher in ccRCC, whereas the frequency of NK cells was higher in oncocytoma. An intratumoral increase of T cell numbers was found with higher tumor grades (G1:G2:G3/4 = 1:3:4). Tumor-associated macrophages slightly increased with dedifferentiation, although the macrophage-to-T cell ratio was highest in G1 tumor lesions. A high expression of CD57 was found in T cells of early tumor grades, whereas T cells in dedifferentiated RCC lesions expressed higher levels of CD69 and CTLA4. TIL composition did not differ between older (>70 y) and younger (<58 y) patients. Enhanced patients' survival was associated with a higher percentage of tumor infiltrating NK cells and Th1 markers, e.g. HLA-DR+ and CXCR3+ T cells, whereas a high number of T cells, especially with high CD69 expression correlated with a worse prognosis of patients. Our results suggest that immunomonitoring of RCC patients might represent a useful tool for the prediction of the outcome of RCC patients.

Keywords: CD13; CD57; CD69; MDSC, myeloid-derived suppressor cells; MFI, mean fluorescence intensity; NK, natural killer cells; PE, phycoerythrine; RCC, renal cell carcinoma; TIL, tumor-infiltrating lymphocytes; flow cytometry; immunohistochemistry; immunophenotype; mAb, monoclonal antibody; oncocytoma; renal cell carcinoma; survival; tumor infiltrating lymphocytes (TIL); tumor-associated macrophages (TAM).