Analysis of Immune Gene Expression Subtypes Reveals Osteosarcoma Immune Heterogeneity

Abstract

Background. Osteosarcoma (OS) patients have a poor response to immunotherapy due to the sheer complexity of the immune system and the nuances of the tumor-immune microenvironment. Methodology. To gain insights into the immune heterogeneity of OS, we identified robust clusters of patients based on the immune gene expression profiles of OS patients in the TARGET database and assessed their reproducibility in an independent cohort collected from the GEO database. The association of comprehensive molecular characterization with reproducible immune subtypes was accessed with ANOVA. Furthermore, we visualized the distribution of individual patients in a tree structure by the graph structure learning-based dimensionality reduction algorithm. Results. We found that 87 OS samples can be divided into 5 immune subtypes, and each of them was associated with distinct clinical outcomes. The immune subtypes also demonstrated widely different patterns in tumor genetic aberrations, tumor-infiltrating, immune cell composition, and cytokine profiles. The immune landscape of OS uncovered the significant intracluster heterogeneity within each subtype and depicted a continuous immune spectrum across patients. Conclusion. The established five immune subtypes in our study suggested immune heterogeneity in OS patients and may provide optimal individual immunotherapy for patients exhibiting OS.

Characterization of the Tumor Microenvironment in Osteosarcoma Identifies Prognostic- and Immunotherapy-Relevant Gene Signatures

“…However, there are studies that have reported opposing findings with regard to the effects of tumor-infiltrating lymphocytes on neoadjuvant chemotherapy responses or prognosis [ 34 ]. This opposing finding could be because tumor-infiltrating lymphocytes are heterogeneous populations [ 35 , 36 ]. The TME heterogeneity affects various responses to clinical therapy; therefore, the TME is a potential biomarker for predicting clinical treatment effects and for screening tumor patients that can benefit from treatment, thereby informing clinical treatment.…”

Identification of Two Novel Immune Subtypes Characterized by Distinct Prognosis and Tumor Microenvironment in Osteosarcoma

“…However, a small part of patients still received a poor survival outcomes [ 21 , 22 ]. With the in-depth recognition of TIME, the differential tumor microenvironment has been confirmed to play an important role in the poor survival outcomes of tumors [ 23 , 24 ]. Therefore, the exploration of TIME is a chance for improving therapeutic effect and prognosis in osteosarcoma.…”

Managing the immune microenvironment of osteosarcoma: the outlook for osteosarcoma treatment

“…Recently, evidence has shown that the body's immune system may be in a constant battle with osteosarcoma cells including three stages: immune clearance, balance, and escape [11][12][13] (Fig. 1).…”