Towards the introduction of the ‘Immunoscore’ in the classification of malignant tumours

The American Joint Committee on Cancer/Union Internationale Contre le Cancer (AJCC/UICC) TNM staging system provides the most reliable guidelines for the routine prognostication and treatment of colorectal carcinoma. This traditional tumour staging summarizes data on tumour burden (T), the presence of cancer cells in draining and regional lymph nodes (N) and evidence for distant metastases (M). However, it is now recognized that the clinical outcome can vary significantly among patients within the same stage. The current classification provides limited prognostic information and does not predict response to therapy. Multiple ways to classify cancer and to distinguish different subtypes of colorectal cancer have been proposed, including morphology, cell origin, molecular pathways, mutation status and gene expression-based stratification. These parameters rely on tumour-cell characteristics. Extensive literature has investigated the host immune response against cancer and demonstrated the prognostic impact of the in situ immune cell infiltrate in tumours. A methodology named ‘Immunoscore’ has been defined to quantify the in situ immune infiltrate. In colorectal cancer, the Immunoscore may add to the significance of the current AJCC/UICC TNM classification, since it has been demonstrated to be a prognostic factor superior to the AJCC/UICC TNM classification. An international consortium has been initiated to validate and promote the Immunoscore in routine clinical settings. The results of this international consortium may result in the implementation of the Immunoscore as a new component for the classification of cancer, designated TNM-I (TNM-Immune). © 2013 The Authors. Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland

Modulation of human tumor associated macrophages from malignant effusions with cytokines and Vobe-Mugos

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Immunoscore as a parameter predicting time to recurrence and disease-free survival in T4N0 stage II colon cancer patients.

4105 Background: Risk assessment is particularly important to decide when to propose an adjuvant treatment for Stage II Colon Cancer (CC) patients. However, the current tumor risk features are imperfect and additional risk factors are needed to guide treatment decisions. The consensus Immunoscore is an alternative and powerful approach that could be used in the T4N0 Stage II colon cancer population. Immunoscore is an in vitro diagnostic test that predicts the risk of relapse in patients with CC by measuring the host immune response at the tumor site. Methods: From the international Immunoscore consortium study (n = 2681) (Pagès et al. The Lancet 2018), a subgroup analysis was performed on T4N0 Stage II colon cancer patients (n = 208). Results: In stage II T4N0, Int+Hi Immunoscore represented 65.4% of the population and low-Immunoscore only 34.6%. T4N0 patients with Int+Hi Immunoscore presented a significantly prolonged survival for TTR compared to low Immunoscore patients (5 years recurrence rate Int+Hi: 84.6% (78.3-91.5), Lo: 46.3% (35.1-61); unadjusted HR [Int+Hi vs Lo] = 0.21; (95% CI 0.11-0.4); P\u3c 0.0001), representing a restricted mean survival time (RMST) difference of 80.9 months (95% CI 51.1-110.6) (P\u3c 0.0001). The DFS was significantly different between Int+Hi and Low Immunoscore (5 years recurrence rate Int+Hi: 70.5% (95% CI 62.7-79.1), Lo: 38.5% (95% CI 28.2-52.5); unadjusted HR [Int+Hi vs Lo] = 0.31; (95% CI 0.19-0.49); P\u3c 0.0001). Using restricted mean survival time (RMST) a significant (P\u3c 0.0001) difference of 60.4 months (95% CI 32.6-88.1) was observed between the 2 groups Importantly, Cox multivariate analysis in Stage II T4N0 colon cancer patients, revealed that Immunoscore was the only remaining significant parameter (HR [Int+Hi vs Lo] = 0.15; (95% CI 0.05-0.46); P= 0.0009). In contrast, all other parameters, gender, sidedness, mucinous, grade, T-stage, VELIPI, MSI were not significant in multivariate analysis. Finally, Immunoscore showed the highest relative contribution to predict relapse (76.2% chi2 relative contribution), stronger than all the other parameters, MSI (16.1%), Grade (5%), sidedness (2%), gender (2%), VELIPI (1%). Conclusions: Immunoscore is the most powerful parameter to predict the risk in T4N0 population, and could be a good tool for adjuvant treatment decision in Stage II patients