Adaptive Immunity in Fibrosarcomatous Dermatofibrosarcoma Protuberans and Response to Imatinib Treatment.
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.
Unit of Immunotherapy of Human Tumors, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Marcella
M
Tazzari
Giorgio Prodi Cancer Research Center, University of Bologna, Bologna, Italy.
Valentina
V
Indio
Consorzio MIA (Microscopy and Image Analysis), University of Milano-Bicocca, Milan, Italy.
Barbara
B
Vergani
Functional Genomics Core Facility, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Loris
L
De Cecco
Unit of Immunotherapy of Human Tumors, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Francesca
F
Rini
Laboratory of Experimental Molecular Pathology, Department of Diagnostic Pathology and Laboratory, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Tiziana
T
Negri
Unit of Immunotherapy of Human Tumors, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Chiara
C
Camisaschi
Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Marco
M
Fiore
Adult Sarcoma Medical Oncology Unit, Department of Cancer Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Silvia
S
Stacchiotti
Laboratory of Experimental Molecular Pathology, Department of Diagnostic Pathology and Laboratory, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
G Paolo
GP
Dagrada
Adult Sarcoma Medical Oncology Unit, Department of Cancer Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Paolo G
PG
Casali
Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Alessandro
A
Gronchi
Giorgio Prodi Cancer Research Center, University of Bologna, Bologna, Italy.
Annalisa
A
Astolfi
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.
Maria A
MA
Pantaleo
Consorzio MIA (Microscopy and Image Analysis), University of Milano-Bicocca, Milan, Italy.
Antonello
A
Villa
Service of Immunohematology & Transfusion Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Claudia
C
Lombardo
Service of Immunohematology & Transfusion Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Flavio
F
Arienti
Laboratory of Experimental Molecular Pathology, Department of Diagnostic Pathology and Laboratory, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Silvana
S
Pilotti
Unit of Immunotherapy of Human Tumors, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Licia
L
Rivoltini
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.
Chiara
C
Castelli
D056704:Adaptive Immunity / Q000187:drug effects*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000032:analysis; D018223:Dermatofibrosarcoma / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D006801:Humans; D000068877:Imatinib Mesylate / Q000627:therapeutic use*; D037181:Lectins, C-Type / Q000032:analysis; D022423:Myeloid Cells / Q000187:drug effects; D011956:Receptors, Cell Surface / Q000032:analysis; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D000970:Antineoplastic Agents; D015815:Cell Adhesion Molecules; D015395:Histocompatibility Antigens Class I; D000068877:Imatinib Mesylate; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin