Abstract 1075: Molecular determinants of colon and renal cancers' immune contextures

Abstract

Abstract In the vast majority of cancer types, as demonstrated and exemplified in colorectal cancer (CRC), a high density of CD8+ T cells in the tumor microenvironment correlates with a good prognosis for the patient. However, an opposite correlation has been reported in primary clear cell renal cell carcinoma (RCC) tumors. Our team studied the immune infiltrates of pulmonary metastases from CRC and RCC. We reported that despite the advanced stage of the disease in these patients, the immune infiltrate of pulmonary metastases remained a prognostic factor. As in the primary tumors, a high density of CD8+ T cells correlated with good prognosis for CRC metastases while it correlated with a bad prognosis for RCC metastases. These results suggest that the identity of the tumor cell is critical in shaping the immune contexture of a given tumor. We therefore investigated the molecular characteristics of the tumor cells which could be responsible for this opposite clinical impact in RCC versus CRC. First, we assessed the prognostic value associated with the expression of genes specific for different immune populations in several cohorts of primary CRC (n=177) and RCC tumors (n=72 and n=479), and confirmed the opposite impact of infiltrating lymphocyte densities on patient survival. In addition, RCC tumors showed a higher expression of genes related to inflammation, immunosuppression and angiogenesis. By comparing transcriptomic data from RCC and CRC cell lines, we observed that RCC tumor cells also expressed a significantly higher amount of these transcripts when compared to CRC tumor cells. Altogether, these results support the hypothesis that RCC malignant cells produce factors which are able to modify and determine the functional orientation of their immune microenvironment. Identifying which factors and pathways are critical for the RCC-related detrimental impact of CD8+ T cells on prognosis will be a major breakthrough, enabling the identification of new immunomodulatory drug targets and guide researchers and clinicians in immunotherapy protocols. Citation Format: Etienne Becht, Nicolas A. Giraldo, Romain Remark, Aurelien de Reynies, Laetitia Lacroix, Diane Damotte, Catherine Sautès-Fridman, Wolf-Herman Fridman. Molecular determinants of colon and renal cancers' immune contextures. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1075. doi:10.1158/1538-7445.AM2014-1075