Immune Biomarkers in Blood from Sarcoma Patients: A Pilot Study

Abstract

The main role of the host immune system is to identify and eliminate cancer cells, which is a complex process, but it is not a fail-safe mechanism. Many sarcoma patients succumb to this disease despite treatments rendered. The aim of this pilot study was to compare the levels of CD4+ T-cells, T-regulatory (Treg) cells, and cytokines such as tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), interleukin-17A (IL-17A), and transforming growth factor-beta-1 (TGF-β1) in peripheral blood leukocytes of sarcoma patients and healthy controls. For gene expression studies, total ribonucleic acid (RNA) was extracted from peripheral blood leukocytes and genes that were differentially regulated in peripheral blood leukocytes of sarcoma patients compared with healthy controls were determined using a commercial T-helper cell differentiation quantitative polymerase chain reaction (qPCR) array. Flow cytometer analysis was performed on blood samples from 26 sarcoma patients and 10 healthy controls to identify the levels of CD4+ T-cells and T-reg cells. The level of cytokines in plasma and culture supernatant were quantified using commercial enzyme-linked immunosorbent assay (ELISA) kits. A marked reduction in the percentage of CD4+ T-cells (p = 0.037) and levels of TNF-α (p = 0.004) and IFN-γ (0.010) was observed in sarcoma patients. Gene expression analysis showed five genes (homeobox A10 (HOXA10), GATA binding protein 3 (GATA3), prostaglandin D2 receptor 2 (PTGDR2), thymocyte selection associated high mobility group box (TOX), and C-C motif chemokine receptor 3 (CCR3)) were dysregulated (p < 0.05) in sarcoma patients. This study suggests that T-helper-1 immune responses are reduced in sarcoma patients.

Transcriptome Sequencing Unveils a Molecular-Stratification-Predicting Prognosis of Sarcoma Associated with Lipid Metabolism

“…In contrast, localized TNF administration using isolated limb perfusion has yielded excellent effects in soft tissue sarcomas [38,39]. A pilot study reported a remarkable decrease in the number of CD4+ T-cells (p = 0.037) and the level of TNF (p = 0.004) in sarcoma patients [40]. It is known that tumor tissues are infiltrated with T cells, monocytes, and other cells producing TNF.…”

Advances in PGD2/PTGDR2 signaling pathway in tumors: A review

“…Moreover, microarray analysis of 1,435 patients revealed that downregulated PGDR2 was related to worse prognosis. In sarcoma, Munisamy et al detected the mRNA level of PTGDR2 and found that its dysregulation was associated with lower survival [89]. Furthermore, oropharyngeal cancer patients with lower PGD2 expression had shorter OS.…”

“…Significantly aberrant expression of 4 genes from the enrichment (including PTGDR2) was associated with lower overall survival in patients [89] Oropharyngeal Enriched, PTGDR1, PTGDR2, and PTGIR genes can be used to screen and evaluate oropharyngeal cancer [90] AML Activation of PTGDR2 is associated with a better prognosis in leukemia patients Activation of PTGDR2 in CyPGs to inhibit the krasmediated MAPK-PI3K/AKT/mTOR signaling pathway to promote apoptosis [52] Prostate Upregulation of PGD2 expression in prostate cancer tissues is associated with higher patient survival compared to normal prostate tissues PGD2 and 15 d-PGJ 2 activate PPAR γ to exert antitumor effects and are involved in tumor microenvironment regulation [121] Liver Enriched PTGDR2 can be a predictor of prognosis in hepatocellular carcinoma [88] Lung…”

Immune Cells in the Tumor Microenvironment of Soft Tissue Sarcomas

“…The CD4+ helper T cells exert antitumor effects by augmenting the cytotoxic T cell functionalities and clonal expansion [53,54]. Although T helper type 1 responses in STSs are considered to be weak [55], the CD4+ TIL counts may exceed those of CD8+, e.g., in differentiated or dedifferentiated retroperitoneal liposarcoma [56]; of note, CD8+ TILs in such TMEs tend to be PD-1+ exhausted.…”