Cancer Phenotypes and their Immune Contextures

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) and several other cancers. Our team studied the immune infiltrates of pulmonary metastases from CRC and RCC metastases. 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 metastasis. These results suggest that the identity of the tumor cells, rather than the organ where they grow, is critical for shaping the immune contexture of a given tumor. We therefore investigated molecular characteristics of the tumor cells, which could be responsible for this difference in prognostic value for RCC and CRC. Subgroups of both RCC and CRC tumors exhibited similar immune contextures , identifying patients with high risk of death, either with low T and B cells infiltrations or, alternatively, high lymphocyte infiltration in the context of a high expression of genes related to inflammation, immunosuppression, and angiogenesis. In CRC, additionally, the MSI-enriched subgroup identifies patients with high cytotoxic T cells infiltration and favorable prognosis. Based on their immune contextures, cancers can therefore be better classified accordingly to their molecular characteristics than their origin.