Modulation of immunosuppressive cells and noncoding RNAs as immunotherapy in osteosarcoma

Abstract

The most common bone cancer is osteosarcoma (OS), which mostly affects children and teenagers. Early surgical resection combined with chemotherapy significantly improves the prognosis of patients with OS. Existing chemotherapies have poor efficacy in individuals with distant metastases or inoperable resection, and these patients may respond better to novel immunotherapies. Immune escape, which is mediated by immunosuppressive cells in the tumour microenvironment (TME), is a major cause of poor OS prognosis and a primary target of immunotherapy. Myeloid-derived suppressor cells, regulatory T cells, and tumour-associated macrophages are the main immunosuppressor cells, which can regulate tumorigenesis and growth on a variety of levels through the interaction in the TME. The proliferation, migration, invasion, and epithelial–mesenchymal transition of OS cells can all be impacted by the expression of non-coding RNAs (ncRNAs), which can also influence how immunosuppressive cells work and support immune suppression in TME. Interferon, checkpoint inhibitors, cancer vaccines, and engineered chimeric antigen receptor (CAR-T) T cells for OS have all been developed using information from studies on the metabolic properties of immunosuppressive cells in TME and ncRNAs in OS cells. This review summarizes the regulatory effect of ncRNAs on OS cells as well as the metabolic heterogeneity of immunosuppressive cells in the context of OS immunotherapies.

Tumor microenvironment phenotypes and prognostic evaluation tools for osteosarcoma characterized by different prognostic outcomes and immunotherapy responses

“…MDSCs and Tregs and TAMs were the main immunosuppressive cells, which could regulate tumorigenesis and growth at many levels through the interaction in TME. 30 There was no significant difference in Tregs and TAMs between samples with low-risk scores and high-risk score, although there was a significant difference in MDSC between the two risk samples. Coupled with the significantly high expression of inhibitory immune checkpoint molecules in samples with low-risk scores, constituting the reason why the low-risk group had better prognosis than the high-risk group.…”

“…Compared with samples showing high‐risk scores, the contents of multiple immune components in TME samples showing low‐risk scores were higher, reflecting the strong immune activity of samples with low‐risk scores. MDSCs and Tregs and TAMs were the main immunosuppressive cells, which could regulate tumorigenesis and growth at many levels through the interaction in TME 30 . There was no significant difference in Tregs and TAMs between samples with low‐risk scores and high‐risk score, although there was a significant difference in MDSC between the two risk samples.…”

m7G-related genes predict prognosis and affect the immune microenvironment and drug sensitivity in osteosarcoma

“…Previous studies have highlighted the involvement of tumor stroma in various processes, including neovascularization, inherent features for tumor homing, microvesicle secretion, paracrine cross-feeding, and immune modulation, all contributing toward tumor progression ( Cortini et al, 2017 ). Additionally, immune cells, such as myeloid-derived suppressor cells, regulatory T cells, and tumor-associated macrophages, have been identified as key players in regulating tumorigenesis and tumor growth ( Xia et al, 2022 ). To explore the impact of m7G modifications on the TME, we used ESTIMATE and MCP counter analyses.…”