Potential of human γδ T cells for immunotherapy of osteosarcoma

Abstract

Recurrent or metastatic osteosarcomas remain a challenging malignancy to treat. Therefore, development and testing of novel therapeutic strategies to target these patients are needed. Adoptive cellular therapy strategies are being evaluated intensively as a novel therapeutic strategy for cancer. Unlike αβ T cells requiring antigen processing and MHC-restricted peptide displayed by antigen-presenting cells, γδ T cells exhibit the potent MHC-unrestricted lytic activity against various tumors in vitro and in vivo. The recent considerable success of γδ T cell-based immunotherapy in lung metastasis of renal cell carcinoma warrants further efforts to apply this treatment to other cancers including osteosarcoma, especially recurrent and metastatic osteosarcomas. In this review, we summarize the available evidence on γδ T cell-based immunotherapy for osteosarcoma that has been achieved to date. More importantly, we discuss potential strategies of the combination of expanded γδ T cells and bisphosphonates, and modification and expansion of αβ TCR modified γδ T cells for improving its efficacy for the treatment of osteosarcoma.

The contribution of immune infiltrates and the local microenvironment in the pathogenesis of osteosarcoma

“…In parallel, PD-1 was expressed in TIL [95] and was increased in peripheral CD4 + and CD8 + T-lymphocytes [96]. Based on these data, the blockade of PD-1/PDL-1 interaction in osteosarcoma-bearing mice led to a decreased tumor burden and an improvement of overall survival [97]. The aberrant expression in osteosarcoma, the expression of PD-1 by TILs and the therapeutic benefit for blocking PD-1/PDL-1 interaction in preclinical models have justified the design of clinical trials.…”

WITHDRAWN: Overexpression of miR-382 sensitizes hepatocellular carcinoma cells to γδ T cells through inhibiting the expression of c-FLIP

“…However, as γδ T cell-based therapy exhibits limited success in cancer treatment [11,12], it suggests that adjuvant therapy is required to improve the efficiency of γδ T cell-based immunotherapy.…”

Clinical value of Pro‑GRP and T lymphocyte subpopulation for the assessment of immune functions of lung cancer patients after DC‑CIK biological therapy

“…DC-CIK cell immune therapy improves the efficacy of traditional chemotherapy or chemoradiotherapy and enhances the anti-tumor effects (24)(25)(26). However, CIK therapy is currently not used for the conventional treatment of lung cancer due to the high individual cost of cell therapy; therefore, the cost of CIK therapy requires to be lowered for it to be provided to a large number of patients.…”