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.

Adaptive Immunity in Fibrosarcomatous Dermatofibrosarcoma Protuberans and Response to Imatinib Treatment / M. Tazzari, V. Indio, B. Vergani, L. De Cecco, F. Rini, T. Negri, C. Camisaschi, M. Fiore, S. Stacchiotti, G.P. Dagrada, P.G. Casali, A. Gronchi, A. Astolfi, M.A. Pantaleo, A. Villa, C. Lombardo, F. Arienti, S. Pilotti, L. Rivoltini, C. Castelli. - In: JOURNAL OF INVESTIGATIVE DERMATOLOGY. - ISSN 0022-202X. - 137:2(2017), pp. 484-493. [10.1016/j.jid.2016.06.634]

Adaptive Immunity in Fibrosarcomatous Dermatofibrosarcoma Protuberans and Response to Imatinib Treatment

M. Tazzari;B. Vergani;T. Negri;C. Camisaschi;M. Fiore;S. Stacchiotti;P.G. Casali;
2017

Abstract

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.
Adaptive Immunity; Antineoplastic Agents; Apoptosis; Cell Adhesion Molecules; Dermatofibrosarcoma; Histocompatibility Antigens Class I; Humans; Imatinib Mesylate; Lectins, C-Type; Myeloid Cells; Receptors, Cell Surface; Skin Neoplasms; T-Lymphocytes; Biochemistry; Molecular Biology; 2708; Cell Biology
Settore MED/06 - Oncologia Medica
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/555652
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