%0 Journal Article
%T Putative contribution of CD56 positive cells in cetuximab treatment efficacy in first-line metastatic colorectal cancer patients
%A RaphaŁżl Mar¨Śchal
%A Jef De Schutter
%A Nathalie Nagy
%A Pieter Demetter
%A Arnaud Lemmers
%A Jacques Devi¨¨re
%A Isabelle Salmon
%A Sabine Tejpar
%A Jean-Luc Van Laethem
%J BMC Cancer
%D 2010
%I BioMed Central
%R 10.1186/1471-2407-10-340
%X We assessed immune cells infiltrate (CD56, CD68, CD3, CD4, CD8, Foxp3) in the primary tumor of metastatic colorectal cancer (mCRC) patients treated with a first-line cetuximab-based chemotherapy in the framework of prospective trials (treatment group) and in a matched group of mCRC patients who received the same chemotherapy regimen without cetuximab (control group). The relationship between intra-tumoral immune effector cells, the K-ras status and the efficacy of the treatment were investigated. We also evaluated in vitro, the ADCC activity in healthy donors and chemonaive mCRC patients and the specific contribution of CD56+ cells.ADCC activity against DLD1 CRC cell line is maintained in cancer patients and significantly declined after CD56+ cells depletion. In multivariate analysis, K-ras wild-type (HR: 4.7 (95% CI 1.8-12.3), p = 0.001) and tumor infiltrating CD56+ cells (HR: 2.6, (95%CI:1.14-6.0), p = 0.019) were independent favourable prognostic factors for PFS and response only in the cetuximab treatment group. By contrast CD56+ cells failed to predict PFS and response in the control group.CD56+ cells, mainly NK cells, may be the major effector of ADCC related-cetuximab activity. Assessment of CD56+ cells infiltrate in primary colorectal adenocarcinoma may provide additional information to K-ras status in predicting response and PFS in mCRC patients treated with first-line cetuximab-based chemotherapy.Cetuximab is a chimeric immunoglobulin G 1 (IgG1) monoclonal antibody (mAb) which binds the epidermal growth factor receptor (EGFR) with high affinity and inhibits ligand binding [1]. Cetuximab is active in chemotherapy resistant metastatic colorectal cancer (mCRC) [2,3] and enhances response rate and progression-free survival (PFS) in first-line therapy in combination with Folfiri and Folfox [4,5]. Clinical studies of cetuximab therapy in mCRC have failed to show a significant correlation between EGFR-staining intensity and patients' response to cetuximab treatme
%U http://www.biomedcentral.com/1471-2407/10/340