This Article Full Text Full Text (PDF) Supplementary Data All Versions of this Article: 0008-5472.CAN-08-2654v1 69/6/2685    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Camus, M. Articles by Galon, J. Search for Related Content PubMed PubMed Citation Articles by Camus, M. Articles by Galon, J.

Coordination of Intratumoral Immune Reaction and Human Colorectal Cancer Recurrence

¹ Integrative Cancer Immunology INSERM AVENIR Team 15, INSERM U872; ² Cordeliers Research Centre, Université Pierre et Marie Curie Paris 6; ³ Université Paris-Descartes; Departments of ⁴ Immunology, ⁵ General and Digestive Surgery, and ⁶ Pathology, Georges Pompidou European Hospital, Paris, France; and ⁷ Institute for Genomics and Bioinformatics, Graz University of Technology, Graz, Austria

Requests for reprints: Jérôme Galon, AVENIR Team 15, Cordeliers Research Centre, INSERM U872, 15 rue de L'Ecole de Médecine, 75006 Paris, France. Phone: 33-1-5310-0404; Fax: 33-1-4051-0420; E-mail: jerome.galon{at}crc.jussieu.fr.

A role for the immune system in controlling the progression of solid tumors has been established in several mouse models. However, the effect of immune responses and tumor escape on patient prognosis in the context of human cancer is poorly understood. Here, we investigate the cellular and molecular parameters that could describe in situ immune responses in human colorectal cancer according to clinical parameters of metastatic lymph node or distant organ invasion (META– or META+ patients). Primary tumor samples of colorectal carcinoma were analyzed by integrating large-scale phenotypic (flow cytometry, 39 patients) and gene expression (real time reverse transcription-PCR, 103 patients) data sets related to immune and protumoral processes. In META– colorectal cancer primary tumors with high densities of T cells, we observed significant positive correlations between markers of innate immune cells [tumor-associated macrophages, dendritic cells, natural killer (NK) cells, and NKT cells] and markers of early-activated T cells. Significant correlations were also observed between markers of cytotoxic and effector memory T-cell subpopulations. These correlation profiles were absent in tumors with low T-cell infiltrates and were altered in META+ tumors with high T-cell infiltrates. We show that the coexpression of genes mediating cytotoxicity (GNLY) and Th1 adaptive immune responses (IRF1) accurately predicted patient survival independently of the metastatic status. High intratumoral mRNA expression of the proangiogenic mediator vascular endothelial growth factor was associated with significantly reduced survival rates in patients expressing high mRNA levels of GNLY. Investigation of the colorectal cancer primary tumor microenvironment allowed us to uncover the association of favorable outcomes with efficient coordination of the intratumoral immune response. [Cancer Res 2009;69(6):2685–93]

This article has been cited by other articles:

				C. Menetrier-Caux, M. Gobert, and C. Caux Differences in Tumor Regulatory T-Cell Localization and Activation Status Impact Patient Outcome Cancer Res., October 15, 2009; 69(20): 7895 - 7898. [Abstract] [Full Text] [PDF]