title: Melan-A/MART-1 immunity in a EWS-ATF1 translocated clear cell sarcoma patient treated with sunitinib: a case report.
abstract: BACKGROUND
  Clear cell sarcoma (CCS), initially named malignant melanoma of soft parts, is an aggressive soft tissue sarcoma (STS) that, due to MITF activation, shares with melanoma the expression of melanocyte differentiation antigens. CCS is poorly sensitive to chemotherapy. Multi-kinase inhibitors have been used as therapeutic agents. In the case we report here, treatment with sunitinib induced a long-lasting clinical response that was associated with an immune activation directed against Melan-A/MART-1 antigen.
  
  
  METHODS
  A 28 years old female patient with an advanced molecularly confirmed CCS resistant to conventional chemotherapy was started in January 2012 on sunitinib, 37.5 mg/day, with evidence of radiologic and metabolic response at the primary and metastatic sites of disease. Pathologic response and loss of the Melan-A/MART-1 antigen were evidenced on residual tumor removed in April 2012. Immunological monitoring performed on patient's blood during pharmacological treatment revealed a systemic, Melan-A/MART-1 specific immunity and a low frequency of immunosuppressive cells. Sunitinib was restarted in May 2012, with a new response, and continued for 11 months although with repeatedly interruptions due to toxicity. Disease progression and new responses were documented at each treatment interruption and restart. Sunitinib was definitively interrupted in April 2013 for disease progression.
  
  
  CONCLUSIONS
  The analysis of this case proves that antigens expressed by CCS, as for melanoma, can be immunogenic in vivo and that tumor-antigen specific T cells may exert anti-tumor activity in CCS patient. Thus, manipulation of the immune response may have therapeutic potential for this STS subtype and immunotherapy approaches, can be promising therapeutic options for these patients.
authors.affiliation: Department of Experimental Oncology and Molecular Medicine, Unit of Immunotherapy of Human Tumours, Milan, Italy. marcella.tazzari@istitutotumori.mi.it.|Fondazione IRCCS Istituto Nazionale dei Tumori, Via G. Venezian 1, Milan, 20133, Italy. marcella.tazzari@istitutotumori.mi.it.
authors.forename: Marcella
authors.initials: M
authors.lastname: Tazzari
authors.affiliation: Department of Cancer Medicine, Adult Sarcoma Medical Oncology Unit, Milan, Italy. elena.palassini@istitutotumori.mi.it.|Fondazione IRCCS Istituto Nazionale dei Tumori, Via G. Venezian 1, Milan, 20133, Italy. elena.palassini@istitutotumori.mi.it.
authors.forename: Elena
authors.initials: E
authors.lastname: Palassini
authors.affiliation: Consorzio MIA (Microscopy and Image Analysis), University of Milano-Bicocca, Milan, Italy. barbara.vergani@unimib.it.
authors.forename: Barbara
authors.initials: B
authors.lastname: Vergani
authors.affiliation: Consorzio MIA (Microscopy and Image Analysis), University of Milano-Bicocca, Milan, Italy. antonello.villa@unimib.it.
authors.forename: Antonello
authors.initials: A
authors.lastname: Villa
authors.affiliation: Department of Experimental Oncology and Molecular Medicine, Unit of Immunotherapy of Human Tumours, Milan, Italy. francesca.rini@istitutotumori.mi.it.|Fondazione IRCCS Istituto Nazionale dei Tumori, Via G. Venezian 1, Milan, 20133, Italy. francesca.rini@istitutotumori.mi.it.
authors.forename: Francesca
authors.initials: F
authors.lastname: Rini
authors.affiliation: Department of Diagnostic Pathology and Laboratory, Laboratory of Experimental Molecular Pathology, Milan, Italy. tiziana.negri2@istitutotumori.mi.it.|Fondazione IRCCS Istituto Nazionale dei Tumori, Via G. Venezian 1, Milan, 20133, Italy. tiziana.negri2@istitutotumori.mi.it.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Negri
authors.affiliation: Department of Surgery, Milan, Italy. chiara.colombo@istitutotumori.mi.it.|Fondazione IRCCS Istituto Nazionale dei Tumori, Via G. Venezian 1, Milan, 20133, Italy. chiara.colombo@istitutotumori.mi.it.
authors.forename: Chiara
authors.initials: C
authors.lastname: Colombo
authors.affiliation: Radiology, Milan, Italy. flavio.crippa@istitutotumori.mi.it.|Fondazione IRCCS Istituto Nazionale dei Tumori, Via G. Venezian 1, Milan, 20133, Italy. flavio.crippa@istitutotumori.mi.it.
authors.forename: Flavio
authors.initials: F
authors.lastname: Crippa
authors.affiliation: Radiology, Milan, Italy. carlo.morosi@istitutotumori.mi.it.|Fondazione IRCCS Istituto Nazionale dei Tumori, Via G. Venezian 1, Milan, 20133, Italy. carlo.morosi@istitutotumori.mi.it.
authors.forename: Carlo
authors.initials: C
authors.lastname: Morosi
authors.affiliation: Department of Cancer Medicine, Adult Sarcoma Medical Oncology Unit, Milan, Italy. paolo.casali@istitutotumori.mi.it.|Fondazione IRCCS Istituto Nazionale dei Tumori, Via G. Venezian 1, Milan, 20133, Italy. paolo.casali@istitutotumori.mi.it.
authors.forename: Paolo G
authors.initials: PG
authors.lastname: Casali
authors.affiliation: Department of Diagnostic Pathology and Laboratory, Laboratory of Experimental Molecular Pathology, Milan, Italy. silvana.pilotti@istitutotumori.mi.it.|Fondazione IRCCS Istituto Nazionale dei Tumori, Via G. Venezian 1, Milan, 20133, Italy. silvana.pilotti@istitutotumori.mi.it.
authors.forename: Silvana
authors.initials: S
authors.lastname: Pilotti
authors.affiliation: Department of Cancer Medicine, Adult Sarcoma Medical Oncology Unit, Milan, Italy. silvia.stacchiotti@istitutotumori.mi.it.|Fondazione IRCCS Istituto Nazionale dei Tumori, Via G. Venezian 1, Milan, 20133, Italy. silvia.stacchiotti@istitutotumori.mi.it.
authors.forename: Silvia
authors.initials: S
authors.lastname: Stacchiotti
authors.affiliation: Department of Experimental Oncology and Molecular Medicine, Unit of Immunotherapy of Human Tumours, Milan, Italy. licia.rivoltini@istitutotumori.mi.it.|Fondazione IRCCS Istituto Nazionale dei Tumori, Via G. Venezian 1, Milan, 20133, Italy. licia.rivoltini@istitutotumori.mi.it.
authors.forename: Licia
authors.initials: L
authors.lastname: Rivoltini
authors.affiliation: Department of Experimental Oncology and Molecular Medicine, Unit of Immunotherapy of Human Tumours, Milan, Italy. chiara.castelli@istitutotumori.mi.it.|Fondazione IRCCS Istituto Nazionale dei Tumori, Via G. Venezian 1, Milan, 20133, Italy. chiara.castelli@istitutotumori.mi.it.
authors.forename: Chiara
authors.initials: C
authors.lastname: Castelli
mesh_terms: D000328:Adult; D000951:Antigens, Neoplasm / Q000276:immunology / Q000378:metabolism; D000970:Antineoplastic Agents / Q000627:therapeutic use; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D007211:Indoles / Q000627:therapeutic use; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000378:metabolism; D058965:MART-1 Antigen / Q000276:immunology*; D009367:Neoplasm Staging; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D049268:Positron-Emission Tomography; D011758:Pyrroles / Q000627:therapeutic use; D018227:Sarcoma, Clear Cell / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology*; D000077210:Sunitinib; D014057:Tomography, X-Ray Computed; D014157:Transcription Factors / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; C111598:EWS-ATF1 fusion protein, human; D007211:Indoles; D058965:MART-1 Antigen; D015514:Oncogene Proteins, Fusion; D011758:Pyrroles; D014157:Transcription Factors; D000077210:Sunitinib