Melan-A/MART-1 immunity in a EWS-ATF1 translocated clear cell sarcoma patient treated with sunitinib: a case report

Abstract

BackgroundClear 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.Case presentationA 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.ConclusionThe 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.

Molecular Determinants of Soft Tissue Sarcoma Immunity: Targets for Immune Intervention

“…Targeted therapy drugs belonging to the anti-angiogenic family, such as sunitinib and pazopanib, have been used for different STS histologies, including solitary fibrous tumors (SFT) and clear cell sarcomas (CSC). In these simple karyotype STSs, we have shown that these drugs modulate systemic and local host immune components [ 55 , 56 , 57 ] and convert the immune TME from “cold” to “hot”. Indeed, sunitinib, by virtue of its effect of the tumor vasculature, promoted an influx of T cells within the previously T cell desert tumor bed.…”

Oncocytic variant of malignant gastrointestinal neuroectodermal tumor: a potential diagnostic pitfall

“…Awareness of this potential pitfall is important, because the clinical behavior of malignant gastrointestinal neuroectodermal tumor and other oncocytic/granular cell tumors of the stomach is quite different, and as there may be some role for targeted therapy in tumors showing EWSR1-ATF1 fusion, which activates potentially targetable downstream effectors including IGFR1, MET, MITF and PDGFR(16)(17)(18)(19).…”

Establishment and Characterization of a Novel Human Clear-cell Sarcoma of Soft-tissue Cell Line, RSAR001, Derived from Pleural Effusion of a Patient with Pleural Dissemination

“…Recent progression in treatments including molecular targeted therapy and immunotherapy for several malignancies, especially for malignant melanoma (20) which has many similarities to CCS (21)(22)(23)(24)(25), has therefore attracted considerable attention for CCS. Although a number of reports indicate the possible efficacy of new therapeutic agents against CCS (23)(24)(25)(26)(27)(28)(29), most are case reports of single cases or a very small number of cases. Therefore, establishing the evidence of efficacy of these agents against CCS, both in basic research and clinically are required.…”