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Immune infiltrates are prognostic factors in localized gastrointestinal stromal tumors

Cancer immunosurveillance relies on effector/memory tumor-infiltrating CD8+ T cells with a T-helper cell 1 (TH1) profile. Evidence for a natural killer (NK) cell-based control of human malignancies is still largely missing. The KIT tyrosine kinase inhibitor imatinib mesylate markedly prolongs the su...

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Main Authors: Rusakiewicz, Sylvie (Author) , Semeraro, Michaela (Author) , Sarabi, Matthieu (Author) , Desbois, Mélanie (Author) , Locher, Clara (Author) , Mendez, Rosa (Author) , Vimond, Nadège (Author) , Concha, Angel (Author) , Garrido, Federico (Author) , Isambert, Nicolas (Author) , Chaigneau, Loic (Author) , Brun-Ly, Valérie Le (Author) , Dubreuil, Patrice (Author) , Cremer, Isabelle (Author) , Caignard, Anne (Author) , Poirier-Colame, Vichnou (Author) , Chaba, Kariman (Author) , Flament, Caroline (Author) , Halama, Niels (Author) , Jäger, Dirk (Author) , Eggermont, Alexander (Author) , Bonvalot, Sylvie (Author) , Commo, Frédéric (Author) , Terrier, Philippe (Author) , Opolon, Paule (Author) , Emile, Jean-François (Author) , Coindre, Jean-Michel (Author) , Kroemer, Guido (Author) , Chaput, Nathalie (Author) , Cesne, Axel Le (Author) , Blay, Jean-Yves (Author) , Zitvogel, Laurence (Author)
Format: Article (Journal)
Language:English
Published: April 16, 2013
In: Cancer research
Year: 2013, Volume: 73, Issue: 12, Pages: 3499-3510
ISSN:1538-7445
DOI:10.1158/0008-5472.CAN-13-0371
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1158/0008-5472.CAN-13-0371
Verlag, lizenzpflichtig, Volltext: https://cancerres.aacrjournals.org/content/73/12/3499
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Author Notes:Sylvie Rusakiewicz, Michaela Semeraro, Matthieu Sarabi, Mélanie Desbois, Clara Locher, Rosa Mendez, Nadège Vimond, Angel Concha, Federico Garrido, Nicolas Isambert, Loic Chaigneau, Valérie Le Brun-Ly, Patrice Dubreuil, Isabelle Cremer, Anne Caignard, Vichnou Poirier-Colame, Kariman Chaba, Caroline Flament, Niels Halama, Dirk Jäger, Alexander Eggermont, Sylvie Bonvalot, Frédéric Commo, Philippe Terrier, Paule Opolon, Jean-François Emile, Jean-Michel Coindre, Guido Kroemer, Nathalie Chaput, Axel Le Cesne, Jean-Yves Blay, and Laurence Zitvogel
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Summary:Cancer immunosurveillance relies on effector/memory tumor-infiltrating CD8+ T cells with a T-helper cell 1 (TH1) profile. Evidence for a natural killer (NK) cell-based control of human malignancies is still largely missing. The KIT tyrosine kinase inhibitor imatinib mesylate markedly prolongs the survival of patients with gastrointestinal stromal tumors (GIST) by direct effects on tumor cells as well as by indirect immunostimulatory effects on T and NK cells. Here, we investigated the prognostic value of tumor-infiltrating lymphocytes (TIL) expressing CD3, Foxp3, or NKp46 (NCR1) in a cohort of patients with localized GIST. We found that CD3+ TIL were highly activated in GIST and were especially enriched in areas of the tumor that conserve class I MHC expression despite imatinib mesylate treatment. High densities of CD3+ TIL predicted progression-free survival (PFS) in multivariate analyses. Moreover, GIST were infiltrated by a homogeneous subset of cytokine-secreting CD56bright (NCAM1) NK cells that accumulated in tumor foci after imatinib mesylate treatment. The density of the NK infiltrate independently predicted PFS and added prognostic information to the Miettinen score, as well as to the KIT mutational status. NK and T lymphocytes preferentially distributed to distinct areas of tumor sections and probably contributed independently to GIST immunosurveillance. These findings encourage the prospective validation of immune biomarkers for optimal risk stratification of patients with GIST. Cancer Res; 73(12); 3499-510. ©2013 AACR.
Item Description:Gesehen am 24.01.2022
Physical Description:Online Resource
ISSN:1538-7445
DOI:10.1158/0008-5472.CAN-13-0371

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