Characteristics and clinical impacts of the immune environments in colorectal and renal cell carcinoma lung metastases: influence of tumor origin
Menée sur des échantillons de métastases pulmonaires prélevés sur des patients atteints d'un carcinome primitif du côlon-rectum ou à cellules rénales, cette étude met en évidence des profils différents des infiltrats immunitaires des métastases en fonction de la localisation de la tumeur primitive
Purpose: If immune cells are involved in tumor surveillance and have a prognostic impact in most primary tumors, little is known about their significance in metastases. Since patient's survival is heterogeneous, even at metastatic stages, we hypothesized that immune cells may be involved in the control of metastases. We therefore characterized the tumor immune microenvironment and its prognostic value in colorectal (CRC) and renal cell carcinoma (RCC) metastases, and compared it to primary tumors. Experimental Design: We analyzed by immunohistochemistry (n=192) and qPCR (n=32) the immune environments of CRC and RCC lung metastases. Results: Metastases from CRC and RCC have different immune infiltrates. Higher densities of DC-LAMP+ mature dendritic cells (P<0.0001) and lower densities of NKp46+ NK cells (P<0.0001) were observed in CRC as compared to RCC metastases, whereas densities of T cells were similar. High densities of CD8+ and DC-LAMP+ cells correlated with longer overall survival (OS) in CRC (P=0.008) and shorter OS in RCC (P<0.0001). High NK cell densities were associated with improved survival in RCC (P=0.002) but not in CRC. Densities of immune cells correlated significantly from primary to relapsing metastases for the same patient. A Th1 orientation was found in CRC metastases, whereas a heterogeneous immune gene expression was found in RCC metastases. Conclusions: Our results demonstrate a major prognostic value of the immune pattern (CD8+/DC-LAMP+ cell densities) in CRC and RCC, reproducible from primary to metastatic tumors, although with opposite clinical impacts, and highlight the role of the tumor cell in shaping its immune environment.