Exploring the landscape of immunotherapy approaches in sarcomas

Abstract

Sarcomas comprise a heterogenous group of malignancies, of more than 100 different entities, arising from mesenchymal tissue, and accounting for 1% of adult malignancies. Surgery, radiotherapy and systemic therapy constitute the therapeutic armamentarium against sarcomas, with surgical excision and conventional chemotherapy, remaining the mainstay of treatment for local and advanced disease, respectively. The prognosis for patients with metastatic disease is dismal and novel therapeutic approaches are urgently required to improve survival outcomes. Immunotherapy, is a rapidly evolving field in oncology, which has been successfully applied in multiple cancers to date. Immunomodulating antibodies, adoptive cellular therapy, cancer vaccines, and cytokines have been tested in patients with different types of sarcomas through clinical trials, pilot studies, retrospective and prospective studies. The results of these studies regarding the efficacy of different types of immunotherapies in sarcomas are conflicting, and the application of immunotherapy in daily clinical practice remains limited. Additional clinical studies are ongoing in an effort to delineate the role of immunotherapy in patients with specific sarcoma subtypes.

Keywords: bone sarcoma; checkpoint inhibitors; immunotherapy; sarcoma; soft tissue sarcoma; undifferentiated pleomorphic sarcoma UPS.

Figure 1

Selected approved and experimental immunotherapy drugs that have been used as single agent or in combination with other treatment modalities in patients with sarcomas. *ChT includes the following regimens: Doxorubicin, AIM (anthracycline, ifosfamide, mesna), AD (anthracycline, dacarbazine), High-dose ifosfamide, Gemcitabine ± Docetaxel or Dacarbazine or Nab-paclitaxel or Vinorelbine, Irinotecan, Liposomal doxorubicin, Metronomic cyclophosphamide. IT, immunotherapy approaches; ICI, immune checkpoint inhibitors; CTLA4, cytotoxic T lymphocyte-associated molecule 4; PD1 programmed death 1; PDL1, programmed death-ligand 1; ACT, adoptive cell therapy; ETC, endogenous T cells; CTL, cytotoxic T lymphocytes; TCR, T-cell receptor; CAR, Chimeric Antigen Receptor; TILs, tumour-infiltrating lymphocytes; NK, natural killer; PHA, phytohemagglutinin; PBL, peripheral blood lymphocytes; IL-2, interleukin-2; ChT, chemotherapy; RT, radiotherapy; T-VEC, Talimogene laherparepvec; Pexa-Vec, pexastimogene devacirepvec.