Current Immunotherapies for Sarcoma: Clinical Trials and Rationale

Abstract

Sarcoma tumors are rare and heterogeneous, yet they possess many characteristics that may facilitate immunotherapeutic responses. Both active strategies including vaccines and passive strategies involving cellular adoptive immunotherapy have been applied clinically. Results of these clinical trials indicate a distinct benefit for select patients. The recent breakthrough of immunologic checkpoint inhibition is being rapidly introduced to a variety of tumor types including sarcoma. It is anticipated that these emerging immunotherapies will exhibit clinical efficacy for a variety of sarcomas. The increasing ability to tailor immunologic therapies to sarcoma patients will undoubtedly generate further enthusiasm and clinical research for this treatment modality.

Validation of a hypoxia related gene signature in multiple soft tissue sarcoma cohorts

“…There is increasing interest in understanding how reduced immune responses promote cancer progression and can be targeted with drugs such as immune checkpoint inhibitors STS [ 30 ]. STS had the largest variation in immune infiltrates (measured by ESTIMATE) of all the cancer types included in TCGA.…”

Managing sarcoma: where have we come from and where are we going?

“…Recently, however, sarcoma research has turned a corner with numerous immunotherapy research initiatives and multiple early-phase clinical trials underway which include cytokine therapies, adoptive cell therapy, therapeutic cancer vaccines and checkpoint inhibitors/immune modulators. 220 , 221 The efficacy of an immune checkpoint inhibitor in sarcomas has only been evaluated by a phase II study that administered ipilimumab, a CTLA-4 inhibitor, to synovial sarcoma patients. However, the study was closed when none of the patients had an objective tumour response 222 , 223 While the checkpoint inhibitor data have been disappointing, it is anticipated that immunotherapies will improve the prognosis of sarcoma patients.…”

“…However, the study was closed when none of the patients had an objective tumour response 222 , 223 While the checkpoint inhibitor data have been disappointing, it is anticipated that immunotherapies will improve the prognosis of sarcoma patients. 224 , 225 …”

Analysis of the immune infiltrate in undifferentiated pleomorphic sarcoma of the extremity and trunk in response to radiotherapy: Rationale for combination neoadjuvant immune checkpoint inhibition and radiotherapy

“…21,22 With recent successes of immunotherapy across multiple solid tumors, there has been increasing interest in applying immunotherapy to the treatment of STS with a small but growing number of immunotherapy clinical trials in advanced sarcomas. [22][23][24][25][26] However, a significant subpopulation of patients treated with immunotherapy will not respond. At baseline, both the tumor immune microenvironment and the poor antigenicity of the tumor allow it to escape immune recognition.…”