Assessing immune infiltration and the tumor microenvironment for the diagnosis and prognosis of sarcoma

Abstract

Background Sarcomas, cancers originating from mesenchymal cells, are comprehensive tumors with poor prognoses, yet their tumorigenic mechanisms are largely unknown. In this study, we characterize infiltrating immune cells and analyze immune scores to identify the molecular mechanism of immunologic response to sarcomas. Method The “CIBERSORT” algorithm was used to calculate the amount of L22 immune cell infiltration in sarcomas. Then, the “ESTIMATE” algorithm was used to assess the “Estimate,” “Immune,” and “Stromal” scores. Weighted gene co-expression network analysis (WGCNA) was utilized to identify the significant module related to the immune therapeutic target. Gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed using the “clusterProfiler” package in R for annotation and visualization. Results Macrophages were the most common immune cells infiltrating sarcomas. The number of CD8 T cells was negatively associated with that of M0 and M2 macrophages, and positively associated with M macrophages in sarcomas samples. The clinical parameters (disease type, gender) significantly increased with higher Estimate, Immune, and Stromal scores, and with a better prognosis. The blue module was significantly associated with CD8 T cells. Functional enrichment analysis showed that the blue module was mainly involved in chemokine signaling and the PI3K-Akt signaling pathway. CD48, P2RY10 and RASAL3 were identified and validated at the protein level. Conclusion Based on the immune cell infiltration and immune microenvironment, three key genes were identified, thus presenting novel molecular mechanisms of sarcoma metastasis.

Construction of a Novel Signature and Prediction of the Immune Landscape in Soft Tissue Sarcomas Based on N6-Methylandenosine-Related LncRNAs

“…Therefore, the activation of NK cells is significantly correlated with better prognosis, while the higher levels of resting NK cells infiltration indicate a worse chance of survival in human malignancies ( Bigley and Simpson, 2015 ; Bisheshar et al, 2020 ). Similarly, the infiltration of M0 macrophages is positively related to poor clinical outcomes in human malignancies, including STS, which aligns with the findings of our study ( Zhu and Hou, 2020 ). Thus, the worse clinical outcomes of the high-risk group may be associated with infiltrating immune cellular populations, and m6A-regulated lncRNAs may function as critical modulators of immune cell infiltration in STS.…”

A CIBERSORTx-based immune cell scoring system could independently predict the prognosis of patients with myelodysplastic syndromes

“…While the enrichment of unpolarized M0 macrophages in the tumor microenvironment has been demonstrated to be detrimental for survival of patients with hepatocellular carcinoma and sarcoma 16,40 , their role in MDS and other hematologic malignancies has been scarcely reported.…”

Development and validation of an immune gene-set based prognostic signature for soft tissue sarcoma

“…Interestingly, Dhupkar et.al indicated that osteosarcoma lung metastases regression by anti-PD1 can be attributed to activated tumor macrophages M1 and reduced macrophages M2 [ 50 ]. Although there are few studies focused on macrophages M0, its relationship with other immune cells, such as CD8 T cells, has also been preliminarily reported [ 51 ]. Natural killer (NK) cells are important immune cells in the innate immune mechanisms.…”