ISY14-5 - Integration of molecular and immune classifications to guide cancer immunotherapies

Abstract

We developped and validated a method called MCP-Counter which allows to simultaneously quantify the proportions of 10 different cellular populations in human tissues and applied it to human cancers. It allowed to establish a microenvironment based classification of cancers that we correlated with known molecular classifications in Colorectal and clear cell Renal Cell Cancers. We confirmed our data by quantifying tumor infiltrating cells by immunohistochemistry. In Colorectal Cancer the molecular and immune classifications confirmed that not only Microsattelite instable (MSI) tumors but also a subgroup of Microsattelite Stable (MSS) tumors are characterized by a favorable immune contexture with high Th1/cytotoxic infiltration. Other subtypes exhibited poor immune infiltation or in the worst prognostic case high T cell infiltration in the context of a major inflammatory angiogenic and desmoplastic reaction which should be addresed differently in terms of immunotherapy. In clear cell Renal Cell Cancer we identified a poor prognosis subgroup with high infiltration of CD8 T cells which express check-point inhibitors in the presence of PDL-1 and or PDL-2 expressing tumor cells. Our analyses form the basis of an unification of molecular and immune classifications of human cancers challenge our current views of the relationship between the composition of the tumor microenvironment and patient prognosis and suggest immunotherapeutic approaches that could benefit subgroups of patients in different cancers.