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Mouna Trabelsi,1,2 Faten Farah,1 Bechir Zouari,3 Mohamed Habib Jaafoura,4 Maher Kharrat1 1Department of Human Genetic (LR99ES10), Faculty of Medicine, University of Tunis El Manar, Tunis 1006, Tunisia; 2Faculty of Sciences, University of Tunis El Manar, Foyer Universitaire, Tunis 2092, Tunisia; 3Department of Preventive Medicine, Faculty of Medicine, University of Tunis El Manar, Tunis 1006, Tunisia; 4Department of Anatomopathology, Faculty of Medicine, University of Tunis El Manar, Tunis 1006, TunisiaCorrespondence: Mouna TrabelsiDepartment of Human Genetic (LR99ES10), Faculty of Medicine, University of Tunis El Manar, 15 Rue Djebel Lakhdhar, Tunis 1006, TunisiaTel +216 51 008 770Email mounatrabelsi@yahoo.frPurpose: The aim of this study was to evaluate the Immunoscore (IS) methodology as a prognostic marker of colorectal adenocarcinoma in Tunisian population. Tumor blocks were retrospectively collected from 106 patients with sporadic colorectal cancer.Methods: Immunohistochemical staining and images analysis software were used to quantify the density of CD3+ and CD8+ tumor-infiltrating lymphocytes in the center of the tumor and invasive margin.Results: The density of CD3+ and CD8+ was significantly associated with 5-year overall survival (P=0.001 and P=0.00098, respectively) and 5-year disease-free survival (P=0.0006 and P=0.0056, respectively). The earlier stage and the absence of vascular emboli showed a significant association with IS analysis. Cox multivariate regression analysis revealed that Immunoscore (from I0 to I4) was more significantly correlated with overall survival (P=0.00011) and disease-free survival (P=0.0008) than Tumor-Node-Metastasis (TNM) staging (P=0.057 and P=0.039, respectively). Patients with low IS were associated with inferior disease-free survival and overall survival, contrary to patients with high IS.Conclusion: This is the first study which evaluated the prognostic value of IS methodology in colorectal cancer in African and Arabic population. The IS methodology carries out in this study allows to estimate the risk of relapse in patients with colorectal cancer. Overall, our results support the implementation of the consensus Immunoscore as a new component for the classification of cancer, designated TNM-Immune.Keywords: colorectal cancer, immunoscore, AJCC/TNM-classification, tumor-infiltrating lymphocytes, digital pathology, immunotherapy

International audience; Therapeutic resistance is a major clinical challenge in oncology. Evidence identifies cancer stem cells (CSCs) as a driver of tumor evolution. Accordingly, the key stemness property unique to CSCs may represent a reservoir of therapeutic target to improve cancer treatment. Here, we carried out a genome-wide RNA interference screen to identify genes that regulate breast CSCs-fate (bCSC). Using an interactome/regulome analysis, we integrated screen results in a functional mapping of the CSC-related processes. This network analysis uncovered potential therapeutic targets controlling bCSC-fate. We tested a panel of 15 compounds targeting these regulators. We showed that mifepristone, salinomycin, and JQ1 represent the best anti-bCSC activity. A combination assay revealed a synergistic interaction of salinomycin/JQ1 association to deplete the bCSC population. Treatment of primary breast cancer xenografts with this combination reduced the tumor-initiating cell population and limited metastatic development. The clinical relevance of our findings was reinforced by an association between the expression of the bCSC-related networks and patient prognosis. Targeting bCSCs with salinomycin/JQ1 combination provides the basis for a new therapeutic approach in the treatment of breast cancer.

Additional file 2: Similar patterns identified between SARS-CoV-2 proteins and antigenic proteins in investigated vaccines.

Additional file 3: Structure of MHC class I heavy chain in complex with Vesicular stomatitis virus nucleoprotein (PDB code 2VAA) [57]. The binding groove floor is composed of 5 strands beta-sheet, resembling the stabilizing beta-sheet from of MSLSLLDLYL peptide within the Measles hemagglutinin Protein.

Additional file 1: Global amino-acid identities between structural protein sequences of SARS-CoV-2 and main antigenic proteins of investigated vaccines.

Additional file 4: List of the HLA alleles used for the prediction of CMH-I binding using IEDB analysis resource.

Additional file 3: Structure of MHC class I heavy chain in complex with Vesicular stomatitis virus nucleoprotein (PDB code 2VAA) [57]. The binding groove floor is composed of 5 strands beta-sheet, resembling the stabilizing beta-sheet from of MSLSLLDLYL peptide within the Measles hemagglutinin Protein.

Additional file 4: List of the HLA alleles used for the prediction of CMH-I binding using IEDB analysis resource.

Additional file 1: Global amino-acid identities between structural protein sequences of SARS-CoV-2 and main antigenic proteins of investigated vaccines.