Metabolomics Monitoring of Treatment Response to Brain Tumor Immunotherapy

Dastmalchi, Farhad; Deleyrolle, Loic P.; Karachi, Aida; Mitchell, Duane A.; Rahman, Maryam

doi:10.3389/fonc.2021.691246

Cited by 21 publications

(12 citation statements)

References 100 publications

(139 reference statements)

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“…Meanwhile, TAMs initiate proinflammatory (M1) or immunosuppressive (M2) function depending on their polarization status. 34 , 35 M2-like macrophage was the main macrophage type that induced immunosuppressive microenvironment and thus accelerated glioma progression. Our results indicated that ARPC1B in macrophages played a tumor-promoting role in glioma malignancy.…”

Section: Discussionmentioning

confidence: 99%

Dual role of ARPC1B in regulating the network between tumor-associated macrophages and tumor cells in glioblastoma

et al. 2022

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The tumor microenvironment (TME) plays a critical role in promoting the growth and metastasis of glioblastoma (GBM). Tumor-associated macrophages (TAMs), the most abundant myeloid cells infiltrating in TME, produce proinflammatory cytokines, regulate glioma cell pools, and lead to GBM progression. Understanding the mechanism of GBM-TAMs regulation can help to find new targeted therapeutic strategies against GBM. Based on the CGGA and TCGA GBM cohorts, ARPC1B was defined as the key macrophage-associated gene with prognostic value. Higher ARPC1B expression was associated with progressive malignancy, poor outcomes and TAM infiltration. We demonstrated that macrophage-expressed ARPC1B promoted the migration, invasion, and epithelial–mesenchymal transition of glioma cells. Glioma-intrinsic ARPC1B also maintained the malignant phenotype and promoted macrophage recruitment. Positive feedback signaling between macrophages and glioma cells via ARPC1B was determined to be under control of the IFNγ-IRF2-ARPC1B axis. This study highlights the important role of ARPC1B in GBM malignancy progression and the regulation network between GBM and TAMs, suggesting ARPC1B as a novel biomarker with potential therapeutic implications.

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Section: Discussionmentioning

confidence: 99%

Dual role of ARPC1B in regulating the network between tumor-associated macrophages and tumor cells in glioblastoma

et al. 2022

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“…Owing to their special metabolic mode, cancer cells tend to utilize glucose and produce excessive lactate even in an environment with a sufficient oxygen supply and release a large amount of lactate into the extracellular microenvironment, thereby causing acidosis, angiogenesis, and immunosuppression simultaneously (58). Consequently, this kind of metabolism modulation breaks the balance of the immune state in the tumor, resulting in an enhanced immunosuppressive effect by promoting the CD4+ CD25+ regulatory T (Treg) cell metabolic profiles and maintaining the acidity of the TME (60). However, excessive lactate attenuates the proliferation of immunocytes, including CD8+ T, natural killer (NK), and dendritic cells (61)(62)(63).…”

Section: Discussionmentioning

confidence: 99%

Identification of Lactate-Related Gene Signature for Prediction of Progression and Immunotherapeutic Response in Skin Cutaneous Melanoma

Xie

Zhang

et al. 2022

Front. Oncol.

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Skin cutaneous melanoma (SKCM) is a skin cancer type characterized by a high degree of immune cell infiltration. The potential function of lactate, a main metabolic product in the tumor microenvironment (TME) of SKCM, remains unclear. In this study, we systemically analyzed the predictive value of lactate-related genes (LRGs) for prognosis and response to immune checkpoint inhibitors (ICIs) in SKCM patients included from The Cancer Genome Atlas (TCGA) database. Cluster 3, by consensus clustering for 61 LRGs, manifested a worse clinical outcome, attributed to the overexpression of malignancy marks. In addition, we created a prognostic prediction model for high- and low-risk patients and verified its performance in a validation cohort, GSE65904. Between TME and the risk model, we found a negative relation of the immunocyte infiltration levels with patients’ risk scores. The low-risk cases had higher ICI expression and could benefit better from ICIs relative to the high-risk cases. Thus, the lactate-related prognosis risk signature may comprehensively provide a basis for future investigations on immunotherapeutic treatment for SKCM.

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“…These changes help cells sustain the high proliferation rate and adapt to continuous fluctuations in the tumor microenvironment, particularly changes in nutrients and oxygen availability (95)(96)(97). Besides, numerous studies suggested a key role of these metabolic adaptations in immune cell dysfunction and cancer immune escape via acidification of the TME, secretion of immunosuppressive cytokines, and induction of epigenetic modifications in immune cells (156)(157)(158). Alongside this, similar metabolic reprogramming occurs on the surrounding immune cells, affecting their activation and function, altering the anti-cancer immunity, and thereby enabling tumor cells to evade the immunosurveillance system (159).…”

Section: Discussionmentioning

confidence: 99%

Metabolic Rewiring in Glioblastoma Cancer: EGFR, IDH and Beyond

et al. 2022

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Glioblastoma multiforme (GBM), a highly invasive and incurable tumor, is the humans’ foremost, commonest, and deadliest brain cancer. As in other cancers, distinct combinations of genetic alterations (GA) in GBM induce a diversity of metabolic phenotypes resulting in enhanced malignancy and altered sensitivity to current therapies. Furthermore, GA as a hallmark of cancer, dysregulated cell metabolism in GBM has been recently linked to the acquired GA. Indeed, Numerous point mutations and copy number variations have been shown to drive glioma cells’ metabolic state, affecting tumor growth and patient outcomes. Among the most common, IDH mutations, EGFR amplification, mutation, PTEN loss, and MGMT promoter mutation have emerged as key patterns associated with upregulated glycolysis and OXPHOS glutamine addiction and altered lipid metabolism in GBM. Therefore, current Advances in cancer genetic and metabolic profiling have yielded mechanistic insights into the metabolism rewiring of GBM and provided potential avenues for improved therapeutic modalities. Accordingly, actionable metabolic dependencies are currently used to design new treatments for patients with glioblastoma. Herein, we capture the current knowledge of genetic alterations in GBM, provide a detailed understanding of the alterations in metabolic pathways, and discuss their relevance in GBM therapy.

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Metabolomics Monitoring of Treatment Response to Brain Tumor Immunotherapy

Cited by 21 publications

References 100 publications

Dual role of ARPC1B in regulating the network between tumor-associated macrophages and tumor cells in glioblastoma

Dual role of ARPC1B in regulating the network between tumor-associated macrophages and tumor cells in glioblastoma

Identification of Lactate-Related Gene Signature for Prediction of Progression and Immunotherapeutic Response in Skin Cutaneous Melanoma

Metabolic Rewiring in Glioblastoma Cancer: EGFR, IDH and Beyond

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