Abstract
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. Because patients' 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 and renal cell carcinoma (RCC) metastases, and compared it to primary tumors. We analyzed by immunohistochemistry (n = 192) and qPCR (n = 32) the immune environments of colorectal carcinoma and RCC lung metastases. Metastases from colorectal carcinoma 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 colorectal carcinoma 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 colorectal carcinoma (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 colorectal carcinoma. Densities of immune cells correlated significantly from primary to relapsing metastases for the same patient. A TH1 orientation was found in colorectal carcinoma metastases, whereas a heterogeneous immune gene expression was found in RCC metastases. Our results show a major prognostic value of the immune pattern (CD8(+)/DC-LAMP(+) cell densities) in colorectal carcinoma 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.
Highlights
Immune cells are found in human solid tumors, and the immune pattern of the tumor microenvironment is a major predictor of patient survival in a large array of primary tumors [1]
A TH1 orientation was found in colorectal carcinoma metastases, whereas a heterogeneous immune gene expression was found in renal cell carcinoma (RCC) metastases
We found that a high infiltration by DC-LAMPþ mature dendritic cells and CD8þ T cells is a major predictor of good survival in lung metastases from colorectal carcinoma, whereas it is associated with poor survival in lung metastases from RCC
Summary
Immune cells are found in human solid tumors, and the immune pattern of the tumor microenvironment is a major predictor of patient survival in a large array of primary tumors [1]. This article demonstrates for the first time, in a large cohort of patients with lung metastasis from 2 different primary tumors, colorectal and renal cell carcinoma, that densities of CD8þ T cells and DC-LAMPþ mature dendritic cells ("immune pattern"), evaluated in paraffin sections, were independent prognostic factors of patients’ survival, and stronger prognosticators than currently evaluated clinical and pathological parameters. Tumor immune environment is reproduced throughout cancer disease, from primary tumor to relapsing metastasis. This finding is the first important step for further extensive studies on the role of the tumor cells in shaping their own immune environment and the patients’ outcome
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