Rational bases for the use of the Immunoscore in routine clinical settings as a prognostic and predictive biomarker in cancer patients

Abstract

The American Joint Committee on Cancer/Union Internationale Contre le Cancer (AJCC/UICC) tumor, nodes, metastasis (TNM) classification system based on tumor features is used for prognosis estimation and treatment recommendations in most cancers. However, the clinical outcome can vary significantly among patients within the same tumor stage and TNM classification does not predict response to therapy. Therefore, many efforts have been focused on the identification of new markers. Multiple tumor cell-based approaches have been proposed but very few have been translated into the clinic. The recent demonstration of the essential role of the immune system in tumor progression has allowed great advances in the understanding of this complex disease and in the design of novel therapies. The analysis of the immune infiltrate by imaging techniques in large patient cohorts highlighted the prognostic impact of the in situ immune cell infiltrate in tumors. Moreover, the characterization of the immune infiltrates (e.g. type, density, distribution within the tumor, phenotype, activation status) in patients treated with checkpoint-blockade strategies could provide information to predict the disease outcome. In colorectal cancer, we have developed a prognostic score ('Immunoscore') that takes into account the distribution of the density of both CD3(+) lymphocytes and CD8(+) cytotoxic T cells in the tumor core and the invasive margin that could outperform TNM staging. Currently, an international retrospective study is under way to validate the Immunoscore prognostic performance in patients with colon cancer. The use of Immunoscore in clinical practice could improve the patients' prognostic assessment and therapeutic management.

Keywords: T cells; colorectal cancer; immune response; lymphocyte; tumor microenvironment.

Fig. 1.

(A) A section of colonic cancer immunostained for CD3, showing the regions of interest (the CT and the IM). (B) An enlargement showing CD3⁺ cells (stained brown) in the stroma and within tumor glands (original magnification ×300). (C) The tumor (shown in red) and the IM (shown in brown) are selected to determine the Immunoscore. (D) The Immunoscore is based on the numeration of CD3⁺ and of CD8⁺ cells in the tumor and the IM. The densities of stained cells are determined using an image analysis workstation. The immune densities are categorized into Hi (high) or Lo (low) in each tumor region, according to a predetermined cutoff value. Patients are stratified according to a score ranging from I0 to I4, depending on the total number of high densities observed (the two markers CD3 and CD8 are assessed in the CT and the two markers are assessed in the IM).