Signal Pathways Involved in the Interaction Between Tumor-Associated Macrophages/TAMs and Glioblastoma Cells

Liu, Xiaojin; Liu, Yuan; Qi, Yiwei; Huang, Yimin; Hu, Feng; Dong, Feihong; Shu, Kai; Lei, Ting

doi:10.3389/fonc.2022.822085

Cited by 8 publications

(5 citation statements)

References 145 publications

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“…Nonetheless, a growing number of investigations have pointed out that different immune cells exhibit different immune functions, which may promote or inhibit the antitumor immune response. CD4 Th2, CD4 Treg, and macrophage M2 are known to be representative immunosuppressive cells that promote cancer growth [ 77 , 78 , 79 ]; hence, we further studied these cells. The risk score was strongly connected to the CD4 Th2 cell infiltration and negatively connected to the CD4 Treg cell infiltration by the ssGSEA algorithm.…”

Section: Discussionmentioning

confidence: 99%

Dynamic Regulation Genes at Microtubule Plus Ends: A Novel Class of Glioma Biomarkers

Wang

Pan

et al. 2023

Biology

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Glioma is the most prevalent and aggressive primary nervous system tumor with an unfavorable prognosis. Microtubule plus-end-related genes (MPERGs) play critical biological roles in the cell cycle, cell movement, ciliogenesis, and neuronal development by coordinating microtubule assembly and dynamics. This research seeks to systematically explore the oncological characteristics of these genes in microtubule-enriched glioma, focusing on developing a novel MPERG-based prognostic signature to improve the prognosis and provide more treatment options for glioma patients. First, we thoroughly analyzed and identified 45 differentially expressed MPERGs in glioma. Based on these genes, glioma patients were well distinguished into two subgroups with survival and tumor microenvironment infiltration differences. Next, we further screened the independent prognostic genes (CTTNBP2, KIF18A, NAV1, SLAIN2, SRCIN1, TRIO, and TTBK2) using 36 prognostic-related differentially expressed MPERGs to construct a signature with risk stratification and prognostic prediction ability. An increased risk score was related to the malignant progression of glioma. Therefore, we also designed a nomogram model containing clinical factors to facilitate the clinical use of the risk signature. The prediction accuracy of the signature and nomogram model was verified using The Cancer Genome Atlas and Chinese Glioma Genome Atlas datasets. Finally, we examined the connection between the signature and tumor microenvironment. The signature positively correlated with tumor microenvironment infiltration, especially immunoinhibitors and the tumor mutation load, and negatively correlated with microsatellite instability and cancer stemness. More importantly, immune checkpoint blockade treatment and drug sensitivity analyses confirmed that this prognostic signature was helpful in anticipating the effect of immunotherapy and chemotherapy. In conclusion, this research is the first study to define and validate an MPERG-based signature closely associated with the tumor microenvironment as a reliable and independent prognostic biomarker to guide personalized choices of immunotherapy and chemotherapy for glioma patients.

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Section: Discussionmentioning

confidence: 99%

Dynamic Regulation Genes at Microtubule Plus Ends: A Novel Class of Glioma Biomarkers

Wang

Pan

et al. 2023

Biology

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“…In this way, TAMs account for one important part of the GBM bulk. TAMs can adopt both M1 and M2 phenotypes in the setting of GBM, but there are a variety of genetic and epigenetic factors that induce the polarization of TAMs toward a stable pro-tumor M2-like phenotype in a hypoxic setting [ 36 ]. Activated microglia release interleukin IL-6 and relevant growth factors, including epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), and transforming growth factor-β (TGF-β), which stimulate glioblastoma cell invasion and angiogenesis [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

A Quantitative Digital Analysis of Tissue Immune Components Reveals an Immunosuppressive and Anergic Immune Response with Relevant Prognostic Significance in Glioblastoma

et al. 2022

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Objectives: Immunostimulatory therapies using immune checkpoint blockers show clinical activity in a subset of glioblastoma (GBM) patients. Several inhibitory mechanisms play a relevant role in the immune response to GBM. With the objective of analyzing the tumor immune microenvironment and its clinical significance, we quantified several relevant immune biomarkers. Design: We studied 76 primary (non-recurrent) GBMs with sufficient clinical follow-up, including a subgroup of patients treated with a dendritic cell vaccine. The IDH-mutation, EGFR-amplification, and MGMT methylation statuses were determined. Several relevant immune biomarkers, including CD163, CD8, PD1, and PDL1, were quantified in representative selected areas by digital image analysis and semiquantitative evaluation. The percentage of each immune expression was calculated with respect to the total number of tumor cells. Results: All GBMs were wild-type IDH, with a subgroup of classical GBMs according to the EGFR amplification (44%). Morphologically, CD163 immunostained microglia and intratumor clusters of macrophages were observed. A significant direct correlation was found between the expression of CD8 and the mechanisms of lymphocyte immunosuppression, in such a way that higher values of CD8 were directly associated with higher values of CD163 (p < 0.001), PDL1 (0.026), and PD1 (0.007). In a multivariate analysis, high expressions of CD8+ (HR = 2.05, 95%CI (1.02–4.13), p = 0.034) and CD163+ cells (HR 2.50, 95%CI (1.29–4.85), p = 0.007), were associated with shorter survival durations. The expression of immune biomarkers was higher in the non-classical (non-EGFR amplified tumors) GBMs. Other relevant prognostic factors were age, receipt of the dendritic cell vaccine, and MGMT methylation status. Conclusions: In accordance with the inverse correlation between CD8 and survival and the direct correlation between effector cells and CD163 macrophages and immune-checkpoint expression, we postulate that CD8 infiltration could be placed in a state of anergy or lymphocytic inefficient activity. Furthermore, the significant inverse correlation between CD163 tissue concentration and survival explains the relevance of this type of immune cell when creating a strong immunosuppressive environment. This information may potentially be used to support the selection of patients for immunotherapy.

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“…Inhibition of CSF-1R (BLZ945) shows the potential to limit glioma progression by repolarizing TAMs into M1 phenotype in mouse GBM models. While in preclinical trials, clinical trials failed to demonstrate effectiveness, partly due to the complicated actions of non-TAMs cells in response to the agents [ 206 ].…”

Section: Exosomes As Drug Delivery Platformmentioning

confidence: 99%

Exosome-based nanoimmunotherapy targeting TAMs, a promising strategy for glioma

et al. 2023

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Exosomes, the cell-derived small extracellular vehicles, play a vital role in intracellular communication by reciprocally transporting DNA, RNA, bioactive protein, chains of glucose, and metabolites. With great potential to be developed as targeted drug carriers, cancer vaccines and noninvasive biomarkers for diagnosis, treatment response evaluation, prognosis prediction, exosomes show extensive advantages of relatively high drug loading capacity, adjustable therapeutic agents release, enhanced permeation and retention effect, striking biodegradability, excellent biocompatibility, low toxicity, etc. With the rapid progression of basic exosome research, exosome-based therapeutics are gaining increasing attention in recent years. Glioma, the standard primary central nervous system (CNS) tumor, is still up against significant challenges as current traditional therapies of surgery resection combined with radiotherapy and chemotherapy and numerous efforts into new drugs showed little clinical curative effect. The emerging immunotherapy strategy presents convincing results in many tumors and is driving researchers to exert its potential in glioma. As the crucial component of the glioma microenvironment, tumor-associated macrophages (TAMs) significantly contribute to the immunosuppressive microenvironment and strongly influence glioma progression via various signaling molecules, simultaneously providing new insight into therapeutic strategies. Exosomes would substantially assist the TAMs-centered treatment as drug delivery vehicles and liquid biopsy biomarkers. Here we review the current potential exosome-mediated immunotherapeutics targeting TAMs in glioma and conclude the recent investigation on the fundamental mechanisms of diversiform molecular signaling events by TAMs that promote glioma progression.

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Signal Pathways Involved in the Interaction Between Tumor-Associated Macrophages/TAMs and Glioblastoma Cells

Cited by 8 publications

References 145 publications

Dynamic Regulation Genes at Microtubule Plus Ends: A Novel Class of Glioma Biomarkers

Dynamic Regulation Genes at Microtubule Plus Ends: A Novel Class of Glioma Biomarkers

A Quantitative Digital Analysis of Tissue Immune Components Reveals an Immunosuppressive and Anergic Immune Response with Relevant Prognostic Significance in Glioblastoma

Exosome-based nanoimmunotherapy targeting TAMs, a promising strategy for glioma

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