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Immunotherapy for synovial sarcoma

1 Seattle Children’s Hospital, University of Washington, Seattle, Washington, USA
2 Department of Pediatrics, University of Washington, Seattle, Washington, USA
3 Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA
4 Department of Medicine, University of Washington, Seattle, Washington, USA

Special Issues: Immunotherapy for Pediatric Malignancies

Synovial sarcoma (SS) is a relatively common subtype of soft tissue sarcoma that typically affects young adults. Nearly all tumors harbor a translocation between SS18 and SSX1/SSX2 and the vast majority express the cancer testis antigen (CTA) NY-ESO-1. While patients with small, non-metastatic tumors are often cured surgically, outcomes remain poor for patients with locally advanced or metastatic disease, even when aggressive chemotherapy and radiotherapy are employed. Therefore, innovative systemic therapies that target the biology of the disease are needed to improve outcomes for these higher risk patients. One such category is tumor-directed immune therapies. In this review, we will discuss the current status of immunotherapy for SS, including the recent trial results, ongoing challenges, and future directions.
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Keywords sarcoma; synovial; immunotherapy; checkpoint inhibitors; NY-ESO-1; adoptive therapy; dendritic cell vaccines

Citation: Catherine M. Albert, Seth Pollack. Immunotherapy for synovial sarcoma. AIMS Medical Science, 2019, 6(3): 191-200. doi: 10.3934/medsci.2019.3.191


  • 1. Riedel RF, Jones RL, Italiano A, et al. (2018) Systemic Anti-Cancer Therapy in Synovial Sarcoma: A Systematic Review. Cancers 10: 417.    
  • 2. Stacchiotti S, Van Tine BA (2018) Synovial Sarcoma: Current Concepts and Future Perspectives. J Clin Oncol 36: 180–187.
  • 3. Kerouanton A, Jimenez I, Cellier C, et al. (2014) Synovial sarcoma in children and adolescents. J Pediatr Hematol Oncol 36: 257–262.    
  • 4. Okcu MF, Despa S, Choroszy M, et al. (2001) Synovial sarcoma in children and adolescents: thirty three years of experience with multimodal therapy. Med Pediatr Oncol 37: 90–96.    
  • 5. de Necochea-Campion R, Zuckerman LM, Mirshahidi HR, et al. (2017) Metastatic biomarkers in synovial sarcoma. Biomark Res 5: 4.    
  • 6. Spillane AJ, A'Hern R, Judson IR, et al. (2000) Synovial sarcoma: a clinicopathologic, staging, and prognostic assessment. J Clin Oncol 18: 3794–3803.    
  • 7. Rosen G, Forscher C, Lowenbraun S, et al. (1994) Synovial sarcoma. Uniform response of metastases to high dose ifosfamide. Cancer 73: 2506–2511.
  • 8. Vlenterie M, Litiere S, Rizzo E, et al. (2016) Outcome of chemotherapy in advanced synovial sarcoma patients: Review of 15 clinical trials from the European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group; setting a new landmark for studies in this entity. Eur J Cancer 58: 62–72.    
  • 9. Kawai A, Araki N, Sugiura H, et al. (2015) Trabectedin monotherapy after standard chemotherapy versus best supportive care in patients with advanced, translocation-related sarcoma: a randomised, open-label, phase 2 study. Lancet Oncol 16: 406–416.    
  • 10. van der Graaf WT, Blay JY, Chawla SP, et al. (2012) Pazopanib for metastatic soft-tissue sarcoma (PALETTE): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet 379: 1879–1886.    
  • 11. Singer S, Baldini EH, Demetri GD, et al. (1996) Synovial sarcoma: prognostic significance of tumor size, margin of resection, and mitotic activity for survival. J Clin Oncol 14: 1201–1208.    
  • 12. Vining CC, Sinnamon AJ, Ecker BL, et al. (2017) Adjuvant chemotherapy in resectable synovial sarcoma. J Surg Oncol 116: 550–558.    
  • 13. Spurrell EL, Fisher C, Thomas JM, et al. (2005) Prognostic factors in advanced synovial sarcoma: an analysis of 104 patients treated at the Royal Marsden Hospital. Ann Oncol 16: 437–444.    
  • 14. Ferrari A, De Salvo GL, Brennan B, et al. (2015) Synovial sarcoma in children and adolescents: the European Pediatric Soft Tissue Sarcoma Study Group prospective trial (EpSSG NRSTS 2005). Ann Oncol 26: 567–572.    
  • 15. Thway K, Fisher C (2014) Synovial sarcoma: defining features and diagnostic evolution. Ann Diagn Pathol 18: 369–380.    
  • 16. Ladanyi M (2001) Fusions of the SYT and SSX genes in synovial sarcoma. Oncogene 20: 5755–5762.    
  • 17. Lai JP, Rosenberg AZ, Miettinen MM, et al. (2012) NY-ESO-1 expression in sarcomas: A diagnostic marker and immunotherapy target. Oncoimmunology 1: 1409–1410.    
  • 18. Schultz-Thater E, Noppen C, Gudat F, et al. (2000) NY-ESO-1 tumour associated antigen is a cytoplasmic protein detectable by specific monoclonal antibodies in cell lines and clinical specimens. Br J Cancer 83: 204–208.    
  • 19. Pardoll DM (2012) The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer 12: 252–264.    
  • 20. Hodi FS, O'Day SJ, McDermott DF, et al. (2010) Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 363: 711–723.    
  • 21. Slovin SF, Higano CS, Hamid O, et al. (2013) Ipilimumab alone or in combination with radiotherapy in metastatic castration-resistant prostate cancer: results from an open-label, multicenter phase I/II study. Ann Oncol 24: 1813–1821.    
  • 22. Lynch TJ, Bondarenko I, Luft A, et al. (2012) Ipilimumab in combination with paclitaxel and carboplatin as first-line treatment in stage IIIB/IV non-small-cell lung cancer: results from a randomized, double-blind, multicenter phase II study. J Clin Oncol 30: 2046–2054.    
  • 23. Topalian SL, Sznol M, McDermott DF, et al. (2014) Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab. J Clin Oncol 32: 1020–1030.    
  • 24. Brahmer JR, Tykodi SS, Chow LQ, et al. (2012) Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med 366: 2455–2465.    
  • 25. Herbst RS, Baas P, Kim DW, et al. (2016) Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet 387: 1540–1550.    
  • 26. Hammers HJ, Plimack ER, Infante JR, et al. (2014) Phase I study of nivolumab in combination with ipilimumab in metastatic renal cell carcinoma (mRCC). J Clin Oncol 25: 361–362.
  • 27. Wolchok JD, Kluger H, Callahan MK, et al. (2013) Nivolumab plus ipilimumab in advanced melanoma. N Engl J Med 369: 122–133.    
  • 28. Hellmann MD, Rizvi NA, Goldman JW, et al. (2017) Nivolumab plus ipilimumab as first-line treatment for advanced non-small-cell lung cancer (CheckMate 012): results of an open-label, phase 1, multicohort study. Lancet Oncol 18: 31–41.    
  • 29. Tawbi HA, Burgess M, Bolejack V, et al. (2017) Pembrolizumab in advanced soft-tissue sarcoma and bone sarcoma (SARC028): a multicentre, two-cohort, single-arm, open-label, phase 2 trial. Lancet Oncol 18: 1493–1501.    
  • 30. D'Angelo SP, Mahoney MR, Van Tine BA, et al. (2018) Nivolumab with or without ipilimumab treatment for metastatic sarcoma (Alliance A091401): two open-label, non-comparative, randomised, phase 2 trials. Lancet Oncol 19: 416–426.    
  • 31. Rizvi NA, Hellmann MD, Snyder A, et al. (2015) Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science 348: 124–128.
  • 32. Snyder A, Makarov V, Merghoub T, et al. (2014) Genetic basis for clinical response to CTLA-4 blockade in melanoma. N Engl J Med 371: 2189–2199.    
  • 33. Tumeh PC, Harview CL, Yearley JH, et al. (2014) PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature 515: 568–571.    
  • 34. McGranahan N, Furness AJ, Rosenthal R, et al. (2016) Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade. Science 351: 1463–1469.    
  • 35. Lazar AJ, McLellan MD, Bailey MH, et al. (2017) Comprehensive and Integrated Genomic Characterization of Adult Soft Tissue Sarcomas. Cell 171: 950–965.    
  • 36. Pollack SM, He Q, Yearley JH, et al. (2017) T-cell infiltration and clonality correlate with programmed cell death protein 1 and programmed death-ligand 1 expression in patients with soft tissue sarcomas. Cancer 123: 3291–3304.    
  • 37. Ni L, Lu J (2018) Interferon gamma in cancer immunotherapy. Cancer Med 7: 4509–4516.    
  • 38. Scanlan MJ, Simpson AJ, Old LJ (2004) The cancer/testis genes: review, standardization, and commentary. Cancer Immun 4: 1.
  • 39. Lai JP, Robbins PF, Raffeld M, et al. (2012) NY-ESO-1 expression in synovial sarcoma and other mesenchymal tumors: significance for NY-ESO-1-based targeted therapy and differential diagnosis. Mod Pathol 25: 854–858.    
  • 40. Satie AP, Rajpert-De Meyts E, Spagnoli GC, et al. (2002) The cancer-testis gene, NY-ESO-1, is expressed in normal fetal and adult testes and in spermatocytic seminomas and testicular carcinoma in situ. Lab Invest 82: 775–780.    
  • 41. Lee DW, Kochenderfer JN, Stetler-Stevenson M, et al. (2015) T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial. Lancet 385: 517–528.    
  • 42. Gardner RA, Finney O, Annesley C, et al. (2017) Intent-to-treat leukemia remission by CD19 CAR T cells of defined formulation and dose in children and young adults. Blood 129: 3322–3331.
  • 43. Srivastava S, Riddell SR (2018) Chimeric Antigen Receptor T Cell Therapy: Challenges to Bench-to-Bedside Efficacy. J Immunol 200: 459–468.    
  • 44. Robbins PF, Morgan RA, Feldman SA, et al. (2011) Tumor regression in patients with metastatic synovial cell sarcoma and melanoma using genetically engineered lymphocytes reactive with NY-ESO-1. J Clin Oncol 29: 917–924.    
  • 45. D'Angelo SP, Melchiori L, Merchant MS, et al. (2018) Antitumor Activity Associated with Prolonged Persistence of Adoptively Transferred NY-ESO-1 (c259)T Cells in Synovial Sarcoma. Cancer Discov 8: 944–957.    
  • 46. Iura K, Maekawa A, Kohashi K, et al. (2017) Cancer-testis antigen expression in synovial sarcoma: NY-ESO-1, PRAME, MAGEA4, and MAGEA1. Hum Pathol 61: 130–139.    
  • 47. Chapman PB, Morrisey D, Panageas KS, et al. (2000) Vaccination with a bivalent G(M2) and G(D2) ganglioside conjugate vaccine: a trial comparing doses of G(D2)-keyhole limpet hemocyanin. Clin Cancer Res 6: 4658–4662.
  • 48. Kawaguchi S, Tsukahara T, Ida K, et al. (2012) SYT-SSX breakpoint peptide vaccines in patients with synovial sarcoma: a study from the Japanese Musculoskeletal Oncology Group. Cancer Sci 103: 1625–1630.    
  • 49. Dillman R, Selvan S, Schiltz P, et al. (2004) Phase I/II trial of melanoma patient-specific vaccine of proliferating autologous tumor cells, dendritic cells, and GM-CSF: planned interim analysis. Cancer Biother Radiopharm 19: 658–665.
  • 50. Dillman RO, Selvan SR, Schiltz PM, et al. (2009) Phase II trial of dendritic cells loaded with antigens from self-renewing, proliferating autologous tumor cells as patient-specific antitumor vaccines in patients with metastatic melanoma: final report. Cancer Biother Radiopharm 24: 311–319.    
  • 51. Steinman RM, Banchereau J (2007) Taking dendritic cells into medicine. Nature 449: 419–426.    
  • 52. Zinkernagel RM (2014) On the Role of Dendritic Cells Versus Other Cells in Inducing Protective CD8+ T Cell Responses. Front Immunol 5: 30.
  • 53. Palucka K, Banchereau J, Mellman I (2010) Designing vaccines based on biology of human dendritic cell subsets. Immunity 33: 464–478.    
  • 54. Santos PM, Butterfield LH (2018) Dendritic Cell-Based Cancer Vaccines. J Immunol 200: 443–449.    
  • 55. Somaiah N, Block MS, Kim JW, et al. (2016) Single-agent LV305 to induce anti-tumor immune and clinical responses in patients with advanced or metastatic sarcoma and other cancers expressing NY-ESO-1. J Clin Oncol 34.
  • 56. Pollack SM (2018) The potential of the CMB305 vaccine regimen to target NY-ESO-1 and improve outcomes for synovial sarcoma and myxoid/round cell liposarcoma patients. Expert Rev Vaccines 17: 107–114.
  • 57. Tareen SU, Kelley-Clarke B, Nicolai CJ, et al. (2014) Design of a novel integration-deficient lentivector technology that incorporates genetic and posttranslational elements to target human dendritic cells. Mol Ther 22: 575–587.    
  • 58. Pollack SM, Lu H, Gnjatic S, et al. (2017) First-in-Human Treatment With a Dendritic Cell-targeting Lentiviral Vector-expressing NY-ESO-1, LV305, Induces Deep, Durable Response in Refractory Metastatic Synovial Sarcoma Patient. J Immunother 40: 302–306.
  • 59. Pollack S, Lu HL, Somaiah N, et al. (2017) Association of CMB305 or LV305-induced and baseline anti-NY-ESO-1 immunity with survival in recurrent cancer patients. J Clin Oncol 35.


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