The future of immunotherapy for sarcoma

ABSTRACT

Introduction: The use of immunotherapeutic challenges for sarcoma has a long history. Despite the existence of objective responses, immunotherapy has been overshadowed by the results of chemotherapy, especially for osteosarcoma. However, the prognosis for non-responders to chemotherapy is still poor and immunotherapy is now focused on again.

Areas covered: We reviewed the following types of clinical trials of immunotherapy for sarcoma: (i) vaccination with autologous tumor cells, (ii) vaccination with peptides derived from tumor-associated antigens, (iii) adoptive cell transfer using engineered T cells expressing T cell receptor directed at NY-ESO-1 and (iv) immune checkpoint inhibitors targeting CTLA-4 and PD1/PDL1.

Expert opinion: The immunogenicity of sarcoma might be lower than that of melanoma. Patients with small lesions who have not received any chemotherapy are good candidates for peptide-based immunotherapy. Combining peptide vaccination and immune checkpoint inhibitors is an attractive option, and long-lived memory T cells are attracting attention. Memory T stem cells defined by CD95+ are long-lived and have the capacity for self-renewal and multidifferentiation. We also identified a novel memory T cell population, young memory T cells defined by CD73+CXCR3+. Regulation of such memory T stem cells will be useful for peptide vaccination and adoptive cell transfer.

KEYWORDS:

• Osteosarcoma
• synovial sarcoma
• peptide vaccination
• immune checkpoint inhibitor
• memory T stem cell

Article highlights

• Vaccination with autologous tumor cells can induce clinical and immunological responses, but the results are not stable.

• Vaccination with antigenic peptides has some efficacy and elicits detectable T cell responses, but the objective response rate is still low.

• Adoptive cell transfer of engineered T cells directed to the cancer-testis antigen NY-ESO-1 results in impressive regression of the sarcoma burden.

• The immune checkpoint inhibitor nivolumab can enhance the immune responses to peptides vaccines.

• Combination therapy with peptide vaccination and immune checkpoint inhibitors for sarcoma is very attractive. Our observations suggest that good responders to vaccination are those with small lesions and without previous chemotherapy.

• Memory stem T cells are attracting more attention with their importance in vaccination and as a source for adoptive cell transfer.

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Declaration of interests

This work was supported by grants from JSPS KAKENHI (25462344 and 16H05451 to T. Tsukahara), the Takeda Science Foundation (2015-Kenkyu-Shorei to T. Tsukahara) and the Cell Science Research Foundation (2016-Kenkyu-Zyosei to T. Tsukahara). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.