Identification of S1PR4 as an immune modulator for favorable prognosis in HNSCC through machine learning

Huang, Chenshen; Zhu, Fengshuo; Zhang, Hao; Wang, Ning; Huang, Qi

doi:10.1016/j.isci.2023.107693

Cited by 4 publications

(2 citation statements)

References 54 publications

(66 reference statements)

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“…In comparison to S1PR1 and S1PR3 effects, S1PR4 was found to be growth-inhibitory in some immune cells [ 175 ], while its role in the lymphocyte trafficking and expansion was extensively discussed [ 169 ]. The receptor may regulate the cytotoxicity of T cells towards cancerous tissues [ 176 ], although downstream signaling pathways of S1PR4 remain largely unclear. S1PR5 was also shown to regulate T cell subtype maturation and functions [ 177 ].…”

Section: Sphingolipids As Mediators Facilitators and Inhibitors Of Tn...mentioning

confidence: 99%

Signaling controversy and future therapeutical perspectives of targeting sphingolipid network in cancer immune editing and resistance to tumor necrosis factor-α immunotherapy

Sukocheva,

Neganova,

Aleksandrova

et al. 2024

Cell Commun Signal

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Anticancer immune surveillance and immunotherapies trigger activation of cytotoxic cytokine signaling, including tumor necrosis factor-α (TNF-α) and TNF-related apoptosis-inducing ligand (TRAIL) pathways. The pro-inflammatory cytokine TNF-α may be secreted by stromal cells, tumor-associated macrophages, and by cancer cells, indicating a prominent role in the tumor microenvironment (TME). However, tumors manage to adapt, escape immune surveillance, and ultimately develop resistance to the cytotoxic effects of TNF-α. The mechanisms by which cancer cells evade host immunity is a central topic of current cancer research. Resistance to TNF-α is mediated by diverse molecular mechanisms, such as mutation or downregulation of TNF/TRAIL receptors, as well as activation of anti-apoptotic enzymes and transcription factors. TNF-α signaling is also mediated by sphingosine kinases (SphK1 and SphK2), which are responsible for synthesis of the growth-stimulating phospholipid, sphingosine-1-phosphate (S1P). Multiple studies have demonstrated the crucial role of S1P and its transmembrane receptors (S1PR) in both the regulation of inflammatory responses and progression of cancer. Considering that the SphK/S1P/S1PR axis mediates cancer resistance, this sphingolipid signaling pathway is of mechanistic significance when considering immunotherapy-resistant malignancies. However, the exact mechanism by which sphingolipids contribute to the evasion of immune surveillance and abrogation of TNF-α-induced apoptosis remains largely unclear. This study reviews mechanisms of TNF-α-resistance in cancer cells, with emphasis on the pro-survival and immunomodulatory effects of sphingolipids. Inhibition of SphK/S1P-linked pro-survival branch may facilitate reactivation of the pro-apoptotic TNF superfamily effects, although the role of SphK/S1P inhibitors in the regulation of the TME and lymphocyte trafficking should be thoroughly assessed in future studies.

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Section: Sphingolipids As Mediators Facilitators and Inhibitors Of Tn...mentioning

confidence: 99%

Signaling controversy and future therapeutical perspectives of targeting sphingolipid network in cancer immune editing and resistance to tumor necrosis factor-α immunotherapy

Sukocheva,

Neganova,

Aleksandrova

et al. 2024

Cell Commun Signal

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“…For example, the computational analysis of multi-omics data helped pinpoint chemokine receptor axes relevant to particular cancer types and, more importantly, the epigenetic mechanisms responsible for their overexpression (Figure 3b) [87]. Beyond cancer types, GPCR expression signatures extracted with ML models have also been shown to allow head and neck cancer patient stratification into subtypes leading to differential sensitivity to immunotherapy [88]. A similar approach enabled the classification of melanoma patients based on survival and response to immunotherapy based on combined GPCR-TME multi-omics data [89].…”

Section: G Protein-coupled Receptorsmentioning

confidence: 99%

Computational Characterization of Membrane Proteins as Anticancer Targets: Current Challenges and Opportunities

Gorostiola González,

Rakers,

Jespers

et al. 2024

IJMS

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Cancer remains a leading cause of mortality worldwide and calls for novel therapeutic targets. Membrane proteins are key players in various cancer types but present unique challenges compared to soluble proteins. The advent of computational drug discovery tools offers a promising approach to address these challenges, allowing for the prioritization of “wet-lab” experiments. In this review, we explore the applications of computational approaches in membrane protein oncological characterization, particularly focusing on three prominent membrane protein families: receptor tyrosine kinases (RTKs), G protein-coupled receptors (GPCRs), and solute carrier proteins (SLCs). We chose these families due to their varying levels of understanding and research data availability, which leads to distinct challenges and opportunities for computational analysis. We discuss the utilization of multi-omics data, machine learning, and structure-based methods to investigate aberrant protein functionalities associated with cancer progression within each family. Moreover, we highlight the importance of considering the broader cellular context and, in particular, cross-talk between proteins. Despite existing challenges, computational tools hold promise in dissecting membrane protein dysregulation in cancer. With advancing computational capabilities and data resources, these tools are poised to play a pivotal role in identifying and prioritizing membrane proteins as personalized anticancer targets.

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A gut commensal protozoan determines respiratory disease outcomes by shaping pulmonary immunity

Burrows,

Ngai,

Chiaranunt

et al. 2024

Cell

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Identification of S1PR4 as an immune modulator for favorable prognosis in HNSCC through machine learning

Cited by 4 publications

References 54 publications

Signaling controversy and future therapeutical perspectives of targeting sphingolipid network in cancer immune editing and resistance to tumor necrosis factor-α immunotherapy

Signaling controversy and future therapeutical perspectives of targeting sphingolipid network in cancer immune editing and resistance to tumor necrosis factor-α immunotherapy

Computational Characterization of Membrane Proteins as Anticancer Targets: Current Challenges and Opportunities

A gut commensal protozoan determines respiratory disease outcomes by shaping pulmonary immunity

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