Natural Killer Cell Interactions With Myeloid Derived Suppressor Cells in the Tumor Microenvironment and Implications for Cancer Immunotherapy

Zalfa, Cristina; Paust, Silke

doi:10.3389/fimmu.2021.633205

Cited by 56 publications

(38 citation statements)

References 468 publications

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“…Concerning TAMs, increased numbers of CD163 + M2 TAMs [130] known to be involved in tumor progression and immune-suppressive functions were detected in almost all EBV-associated malignancies [130,145,149] and were mainly distributed in the stroma. In addition, myeloid-derived suppressor cells (MDSCs) with immune regulatory properties are expanded in EBV-positive tumors, such as NPCs [161], and have a potent immunesuppressive activity sustaining an anti-inflammatory TME by suppressing T-cell effector functions [150,162]. Next to their presence in the stroma, circulating MDSCs were detected in the PBMCs of HL, NPC and GC patients [163][164][165].…”

Section: Cellular Composition Of the Tmementioning

confidence: 99%

Epstein–Barr Virus—Associated Malignancies and Immune Escape: The Role of the Tumor Microenvironment and Tumor Cell Evasion Strategies

Bauer

Jasinski‐Bergner

Mandelboim

et al. 2021

Cancers

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The detailed mechanisms of Epstein–Barr virus (EBV) infection in the initiation and progression of EBV-associated malignancies are not yet completely understood. During the last years, new insights into the mechanisms of malignant transformation of EBV-infected cells including somatic mutations and epigenetic modifications, their impact on the microenvironment and resulting unique immune signatures related to immune system functional status and immune escape strategies have been reported. In this context, there exists increasing evidence that EBV-infected tumor cells can influence the tumor microenvironment to their own benefit by establishing an immune-suppressive surrounding. The identified mechanisms include EBV gene integration and latent expression of EBV-infection-triggered cytokines by tumor and/or bystander cells, e.g., cancer-associated fibroblasts with effects on the composition and spatial distribution of the immune cell subpopulations next to the infected cells, stroma constituents and extracellular vesicles. This review summarizes (i) the typical stages of the viral life cycle and EBV-associated transformation, (ii) strategies to detect EBV genome and activity and to differentiate various latency types, (iii) the role of the tumor microenvironment in EBV-associated malignancies, (iv) the different immune escape mechanisms and (v) their clinical relevance. This gained information will enhance the development of therapies against EBV-mediated diseases to improve patient outcome.

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Section: Cellular Composition Of the Tmementioning

confidence: 99%

Epstein–Barr Virus—Associated Malignancies and Immune Escape: The Role of the Tumor Microenvironment and Tumor Cell Evasion Strategies

Bauer

Jasinski‐Bergner

Mandelboim

et al. 2021

Cancers

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“…In addition, we illustrated that the positive correlation between KDM1A expression and MDSC infiltration happened in most cancers. MDSCs, as a heterogeneous group of myeloid cells, own potent immunosuppressive activity via interacting with innate and adaptive immune cells and perform a significant role in modulating antitumor immunity [ 48 ]. For adaptive immune cells, a statistically negative correlation was shown between KDM1A expression and CD 8+ T cell infiltration in TGCT, LGG, KIRP, KIRC, and HNSC-HPV + .…”

Section: Discussionmentioning

confidence: 99%

KDM1A Identified as a Potential Oncogenic Driver and Prognostic Biomarker via Multi-Omics Analysis

Wang

Mou

et al. 2021

Canadian Journal of Infectious Diseases and Medical Microbiolog

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Background. Lysine-specific demethylase 1A (KDM1A) is a histone demethylation enzyme and a crucial epigenetic factor for multiple pathological pathways that mediate carcinogenesis and immunogenicity. Although increasing evidence supposes the association between KDM1A and cancers, no systematic multi-omics analysis of KDM1A is available. Methods. We systematically evaluated the KDM1A expression of various cancer and normal tissues and the unique relationship between KDM1A expression and prognosis of cancer cases based on The Cancer Genome Atlas (TCGA), Genotype Tissue Expression (GTEx), and Clinical Proteomic Tumor Analysis Consortium (CPTAC) database. The genetic variations, phosphorylation, and DNA methylation of KDM1A were analyzed via various tools. We further analyzed the correlation of KDM1A expression and fibroblasts and immune cell infiltration score of TCGA samples via TIMER2.0. Results. KDM1A was highly expressed in 17 types of total 33 cancers, while it expressed low levels in only 4 cancers. High KDM1A expression was associated with worse survival status in various cancers. KDM1A expression was positively correlated with the cancer-associated fibroblasts and myeloid-derived suppressor cells infiltration levels in most cancer types. Additionally, KDM1A in most cancer types was negatively correlated with Th1 cell infiltration and positively correlated with Th2 cells. Moreover, spliceosome, cell cycle, and RNA transport pathways were involved in the functional mechanisms of KDM1A via enrichment analysis. Conclusions. Our study describes the epigenetic factor KDM1A as an oncogene and prognostic biomarker. Our findings provide valuable guidance for further analysis of KDM1A function in pathogenesis and potential clinical treatment.

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“…Metabolic obstacles including hypoxia, low pH, and depletion of essential nutrients such as amino acids and glucose, are common features of the solid tumour microenvironment (TME) that can markedly suppress immune cell function [ 36 , 37 , 38 ]. Further obstacles are posed by immunosuppressive cell types such as tumour-associated macrophages (TAMs), T regulatory cells (Tregs), and myeloid-derived suppressor cells (MDCSs) [ 39 , 40 ]; these cells express high levels of immune inhibitory molecules, such as programmed death receptor ligands (PD-L1 and PD-L2), galectin-9, and the so-called herpes virus entry mediator (HVEM), and secrete large amounts of anti-inflammatory cytokines, including transforming growth factor-β (TGF-β and interleukin (IL)-10 [ 39 , 41 , 42 , 43 , 44 , 45 , 46 , 47 ].…”

Section: Solid Tumour Targeting By Engineered Immune Cellsmentioning

confidence: 99%

Payload Delivery: Engineering Immune Cells to Disrupt the Tumour Microenvironment

Fowler

Nattress

Navarrete

et al. 2021

Cancers

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Although chimeric antigen receptor (CAR) T cells have shown impressive clinical success against haematological malignancies such as B cell lymphoma and acute lymphoblastic leukaemia, their efficacy against non-haematological solid malignancies has been largely disappointing. Solid tumours pose many additional challenges for CAR T cells that have severely blunted their potency, including homing to the sites of disease, survival and persistence within the adverse conditions of the tumour microenvironment, and above all, the highly immunosuppressive nature of the tumour milieu. Gene engineering approaches for generating immune cells capable of overcoming these hurdles remain an unmet therapeutic need and ongoing area of research. Recent advances have involved gene constructs for membrane-bound and/or secretable proteins that provide added effector cell function over and above the benefits of classical CAR-mediated cytotoxicity, rendering immune cells not only as direct cytotoxic effectors against tumours, but also as vessels for payload delivery capable of both modulating the tumour microenvironment and orchestrating innate and adaptive anti-tumour immunity. We discuss here the novel concept of engineered immune cells as vessels for payload delivery into the tumour microenvironment, how these cells are better adapted to overcome the challenges faced in a solid tumour, and importantly, the novel gene engineering approaches required to deliver these more complex polycistronic gene constructs.

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Natural Killer Cell Interactions With Myeloid Derived Suppressor Cells in the Tumor Microenvironment and Implications for Cancer Immunotherapy

Cited by 56 publications

References 468 publications

Epstein–Barr Virus—Associated Malignancies and Immune Escape: The Role of the Tumor Microenvironment and Tumor Cell Evasion Strategies

Epstein–Barr Virus—Associated Malignancies and Immune Escape: The Role of the Tumor Microenvironment and Tumor Cell Evasion Strategies

KDM1A Identified as a Potential Oncogenic Driver and Prognostic Biomarker via Multi-Omics Analysis

Payload Delivery: Engineering Immune Cells to Disrupt the Tumour Microenvironment

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