Adaptive Immunity in Fibrosarcomatous Dermatofibrosarcoma Protuberans and Response to Imatinib Treatment.

Autor: Tazzari M; Unit of Immunotherapy of Human Tumors, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Indio V; Giorgio Prodi Cancer Research Center, University of Bologna, Bologna, Italy., Vergani B; Consorzio MIA (Microscopy and Image Analysis), University of Milano-Bicocca, Milan, Italy., De Cecco L; Functional Genomics Core Facility, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Rini F; Unit of Immunotherapy of Human Tumors, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Negri T; Laboratory of Experimental Molecular Pathology, Department of Diagnostic Pathology and Laboratory, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Camisaschi C; Unit of Immunotherapy of Human Tumors, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Fiore M; Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Stacchiotti S; Adult Sarcoma Medical Oncology Unit, Department of Cancer Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Dagrada GP; Laboratory of Experimental Molecular Pathology, Department of Diagnostic Pathology and Laboratory, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Casali PG; Adult Sarcoma Medical Oncology Unit, Department of Cancer Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Gronchi A; Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Astolfi A; Giorgio Prodi Cancer Research Center, University of Bologna, Bologna, Italy., Pantaleo MA; Giorgio Prodi Cancer Research Center, University of Bologna, Bologna, Italy; Department of Specialized, Experimental and Diagnostic Medicine, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy., Villa A; Consorzio MIA (Microscopy and Image Analysis), University of Milano-Bicocca, Milan, Italy., Lombardo C; Service of Immunohematology & Transfusion Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Arienti F; Service of Immunohematology & Transfusion Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Pilotti S; Laboratory of Experimental Molecular Pathology, Department of Diagnostic Pathology and Laboratory, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Rivoltini L; Unit of Immunotherapy of Human Tumors, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Castelli C; Unit of Immunotherapy of Human Tumors, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. Electronic address: chiara.castelli@istitutotumori.mi.it.
Jazyk: angličtina
Zdroj: The Journal of investigative dermatology [J Invest Dermatol] 2017 Feb; Vol. 137 (2), pp. 484-493. Date of Electronic Publication: 2016 Sep 05.
DOI: 10.1016/j.jid.2016.06.634
Abstrakt: Dermatofibrosarcoma protuberans (DFSP), although rare, is the most frequent skin sarcoma. Here, we focus on DFSP carrying the fibrosarcomatous transformation (FS-DFSP). FS-DFSP responds to imatinib (IM); however, tumor relapse often occurs. In a series of 21 pre- and post-treatment FS-DFSP samples, the present study explored the events that occur at the tumor site during IM therapy. Gene expression profile and immunohistochemistry analyses documented the occurrence of IM-induced senescence phenotype in the tumor cells and showed the accumulation of activated CD3 + T cells and CD163 + CD14 + myeloid cells expressing the CD209 marker in post-therapy lesions. In post-IM specimens, the pathological response and tumor apoptosis were tightly associated with T-cell infiltration, thus suggesting the presence of an ongoing anti-tumor response, which was further confirmed by in vitro functional assays with CD3 + T cells isolated from an IM-responding FS-DFSP lesion. The integration of targeted therapies with immune therapies is currently under investigation to achieve longer tumor control. Our data outline the in situ immunological effects of IM and classify IM-treated FS-DFSP as potentially sensitive to immunotherapy, thus providing the rationale for further investigations of combination treatment for this soft-tissue sarcoma.
(Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE