Professional killers: The role of extracellular vesicles in the reciprocal interactions between natural killer, CD8+ cytotoxic T‐cells and tumour cells

Vecchio, Filippo Del; Martinez-Rodriguez, Verena; Schukking, Monique; Cocks, Alexander; Broseghini, Elisabetta; Fabbri, Muller

doi:10.1002/jev2.12075

Cited by 38 publications

(32 citation statements)

References 161 publications

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“…Subsequently, we found differences in immune characteristics between subtypes. Professional killer cells include NK and CD8+ T cells, which represent some of the most effective immune defense mechanisms against cancer cells; stromal CD8+ T cell density has independent prognostic impact in resected NSCLC and is a good candidate marker (34,35). Tregs can suppress the activation of the immune system, maintain immune tolerance to self-antigens, and contribute to immunosuppression of antitumor immunity, which is critical for tumor immune evasion in epithelial malignancies, including lung cancer (36).…”

Section: Discussionmentioning

confidence: 99%

Signatures of Multi-Omics Reveal Distinct Tumor Immune Microenvironment Contributing to Immunotherapy in Lung Adenocarcinoma

Huang

Guo

et al. 2021

Front. Immunol.

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BackgroundLung adenocarcinoma (LUAD) contains a variety of genomic and epigenomic abnormalities; the effective tumor markers related to these abnormalities need to be further explored.MethodsClustering analysis was performed based on DNA methylation (MET), DNA copy number variation (CNV), and mRNA expression data, and the differences in survival and tumor immune microenvironment (TIME) between subtypes were compared. Further, we evaluated the signatures in terms of both prognostic value and immunological characteristics.ResultsThere was a positive correlation between MET and CNV in LUAD. Integrative analysis of multi-omics data from 443 samples determined molecular subtypes, iC1 and iC2. The fractions of CD8+ T cells and activated CD4+ T cells were higher, the fraction of Tregs was lower, and the expression level of programmed death-ligand 1 (PD-L1) was higher in iC2 with a poor prognosis showing a higher TIDE score. We selected PTTG1, SLC2A1, and FAM83A as signatures of molecular subtypes to build a prognostic risk model and divided patients into high-risk group and low-risk group representing poor prognosis and good prognosis, respectively, which were validated in 180 patients with LUAD. Further, the low-risk group with lower TIDE score had more infiltrating immune cells. In 100 patients with LUAD, the high-risk group with an immunosuppressive state had a higher expression of PD-L1 and lower counts of CD8+ T cells and dendritic cells.ConclusionsThese findings demonstrated that combined multi-omics data could determine molecular subtypes with significant differences of prognosis and TIME in LUAD and suggested potent utility of the signatures to guide immunotherapy.

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Section: Discussionmentioning

confidence: 99%

Signatures of Multi-Omics Reveal Distinct Tumor Immune Microenvironment Contributing to Immunotherapy in Lung Adenocarcinoma

Huang

Guo

et al. 2021

Front. Immunol.

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“…by TCR activation ( 66 ). Since the putative role of exosomes and their cargo proteins in the regulation of T cell-mediated immune responses and autoimmune diseases has been recently reviewed by Anel and co-workers ( 67 ) and Del Vecchio and colleagues comprehensively reviewed the role of extracellular vesicles in the interactions between NK cells and CD8 + CTL and tumor cells ( 68 ), we will focus on the potential relationship between intra- and extracellular vesicles in the following. The basis for the close relationship of intra- and extracellular vesicles is the common origin of secretory lysosomes and exosomes from cytoplasmic MVBs.…”

Section: Conceptually Intra- and Extracellular Vesicles Should Not Be Separatedmentioning

confidence: 99%

Intra- and Extracellular Effector Vesicles From Human T And NK Cells: Same-Same, but Different?

Lettau

Janßen

2021

Front. Immunol.

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Cytotoxic T lymphocytes (CTL) and Natural Killer (NK) cells utilize an overlapping effector arsenal for the elimination of target cells. It was initially proposed that all cytotoxic effector proteins are stored in lysosome-related effector vesicles (LREV) termed “secretory lysosomes” as a common storage compartment and are only released into the immunological synapse formed between the effector and target cell. The analysis of enriched LREV, however, revealed an uneven distribution of individual effectors in morphologically distinct vesicular entities. Two major populations of LREV were distinguished based on their protein content and signal requirements for degranulation. Light vesicles carrying FasL and 15 kDa granulysin are released in a PKC-dependent and Ca2+-independent manner, whereas dense granules containing perforin, granzymes and 9 kDa granulysin require Ca2+-signaling as a hallmark of classical degranulation. Notably, both types of LREV do not only contain the mentioned cytolytic effectors, but also store and transport diverse other immunomodulatory proteins including MHC class I and II, costimulatory and adhesion molecules, enzymes (i.e. CD26/DPP4) or cytokines. Interestingly, the recent analyses of CTL- or NK cell-derived extracellular vesicles (EV) revealed the presence of a related mixture of proteins in microvesicles or exosomes that in fact resemble fingerprints of the cells of origin. This overlapping protein profile indicates a direct relation of intra- and extracellular vesicles. Since EV potentially also interact with cells at distant sites (apart from the IS), they might act as additional effector vesicles or intercellular communicators in a more systemic fashion.

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“…They can meditate crosstalk between immunity and regulate cancer progression. First, B cell-derived exosomes were identified, and then it was found that lymphocytes, dendritic cells (DCs), natural killer cells, mast cells, macrophages, and thymocytes can all produce exosomes [123]. Yan et al has demonstrated that the exosomes of various immune cells contain their origins, target cells, consequences, and involved molecules [124].…”

Section: Role Of Evs In Colorectal Tumorigenesismentioning

confidence: 99%

Exosomal Components and Modulators in Colorectal Cancer: Novel Diagnosis and Prognosis Biomarkers

Chang

Chan

et al. 2021

Biomedicines

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The relatively high incidence and mortality rates for colorectal carcinoma (CRC) make it a formidable malignant tumor. Comprehensive strategies have been applied to predict patient survival and diagnosis. Various clinical regimens have also been developed to improve the therapeutic outcome. Extracellular vesicles (EVs) are recently proposed cellular structures that can be produced by natural or artificial methods and have been extensively studied. In addition to their innate functions, EVs can be manipulated to be drug carriers and exert many biological functions. The composition of EVs, their intravesicular components, and the surrounding tumor microenvironment are closely related to the development of colorectal cancer. Determining the expression profiles of exocytosis samples and using them as indicators for selecting effective combination therapy is an indispensable direction for EV study and should be regarded as a novel prediction platform in addition to cancer stage, prognosis, and other clinical assessments. In this review, we summarize the function, regulation, and application of EVs in the colon cancer research field. We provide an update on and discuss potential values for clinical applications of EVs. Moreover, we illustrate the specific markers, mediators, and genetic alterations of EVs in colorectal carcinogenesis. Furthermore, we outline the vital markers present in the EVs and discuss their plausible uses in colon cancer patient therapy in combination with the currently used clinical strategies. The development and application of these EVs will significantly improve the accuracy of diagnosis, lead to more precise prognoses, and may lead to the improved treatment of colorectal cancer.

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Professional killers: The role of extracellular vesicles in the reciprocal interactions between natural killer, CD8+ cytotoxic T‐cells and tumour cells

Cited by 38 publications

References 161 publications

Signatures of Multi-Omics Reveal Distinct Tumor Immune Microenvironment Contributing to Immunotherapy in Lung Adenocarcinoma

Signatures of Multi-Omics Reveal Distinct Tumor Immune Microenvironment Contributing to Immunotherapy in Lung Adenocarcinoma

Intra- and Extracellular Effector Vesicles From Human T And NK Cells: Same-Same, but Different?

Exosomal Components and Modulators in Colorectal Cancer: Novel Diagnosis and Prognosis Biomarkers

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