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Abstract
To determine whether the tumor immune infiltrate, as recently evaluated with the Immunoscore methodology, could be a useful prognostic marker in patients with rectal cancers. The influence of the immune infiltrate on patient's outcome was investigated in patients with or without preoperative chemoradiation therapy (pCRT). The density of total (CD3(+)) and cytotoxic (CD8(+)) T lymphocytes was evaluated by immunohistochemistry and quantified by a dedicated image analysis software in surgical specimens of patients with rectal cancer (n = 111) who did not receive pCRT and in tumor biopsies performed before pCRT from additional 55 patients. The results were correlated with tumor recurrence, patient's survival, and response to pCRT. The densities of CD3(+) and CD8(+) lymphocytes and the associated Immunoscore (from I0 to I4) were significantly correlated with differences in disease-free and overall survival (HR, 1.81 and 1.72, respectively; all P < 0.005). Cox multivariate analysis supports the advantage of the Immunoscore compared with the tumor-node-metastasis (TNM) staging in predicting recurrence and survival (all P < 0.001). Lymph node ratio added information in a prognostic model (all P < 0.05). In addition, high infiltration of CD3(+) and CD8(+) lymphocytes in tumor biopsies was associated with downstaging of the tumor after pCRT (CD3(+) cells; Fisher exact test P = 0.01). The Immunoscore could be a useful prognostic marker in patients with rectal cancer treated by primary surgery. The determination of the immune infiltrate in biopsies before treatment could be a valuable information for the prediction of response to pCRT.
Highlights
In rectal cancers, the worldwide used American Joint Committee on Cancer/Unio Internationale Contra Cancrum tumor–node-metastasis (AJCC/UICC-TNM) systemAuthors' Affiliations: 1Department of Surgery, University of Medicine and Pharmacy "Gr T Popa"; Departments of 2Pathology and 3Surgical Oncology, Regional Institute of Oncology; 4Department of Pathology St
The determination of the immune infiltrate in biopsies before treatment could be a valuable information for the prediction of response to preoperative chemoradiation therapy (pCRT)
We demonstrated that the immune infiltrate within colorectal tumors strongly influenced the outcome of patients with colorectal cancer
Summary
In rectal cancers, the worldwide used American Joint Committee on Cancer/Unio Internationale Contra Cancrum tumor–node-metastasis (AJCC/UICC-TNM) systemAuthors' Affiliations: 1Department of Surgery, University of Medicine and Pharmacy "Gr T Popa"; Departments of 2Pathology and 3Surgical Oncology, Regional Institute of Oncology; 4Department of Pathology St. Spiridon Hospital, Iasi, Romania; 5Department of General and Digestive Surgery of the Georges Pompidou European Hospital and 6Department of Pathology of the Georges Pompidou European Hospital, 7Laboratory of Immunology, Immunomonitoring platform of the Georges Pompidou European Hospital, AP-HP; 8Laboratory of Integrative Cancer Immunology, Institut national de la sante et de la recherche medicale (INSERM) U872, Cordeliers Research Center; 9Paris-Descartes University; 10Pierre et Marie Curie-Paris 6 University, Paris; and 11Department of Pathology, Avicenne Hospital, Bobigny, FranceNote: Supplementary data for this article are available at Clinical Cancer Research Online (http://clincancerres.aacrjournals.org/).M.-G. Anitei, G. Zeitoun, and B. Mlecnik contributed equally to this work.
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