Oncologic Trogocytosis of an Original Stromal Cells Induces Chemoresistance of Ovarian Tumours

Rafii, Arash; Mirshahi, Pezhman; Poupot, Mary; Faussat, Anne-Marie; Simon, Anne; Ducros, Elodie; Mery-Lamarche, Eliane; Couderc, Bettina; Lis, Raphaël; Capdet, J.; Bergalet, Julie; Querleu, Denis; Dagonnet, Francoise; Fournié, Jean‐Jacques; Marie, Jean‐Pierre; Pujade-Lauraine, Éric; Favre, Gilles; Soria, J; Mirshahi, Massoud

doi:10.1371/journal.pone.0003894

Cited by 85 publications

(106 citation statements)

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“…In addition, the uptake of multidrug resistance proteins by ovarian cancer cells resulted in decreased sensitivity of tumor cells toward chemotherapeutic drugs (17). Together, these data implicate that trogocytosis plays an important role in the modulation of cellular immune responses.…”

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confidence: 82%

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Antigen-Specific Transfer of Functional Programmed Death Ligand 1 from Human APCs onto CD8+ T Cells via Trogocytosis

Gary

Voelkl

Palmisano³

et al. 2012

The Journal of Immunology

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Upon specific interaction with APCs, T cells capture membrane fragments and surface molecules in a process termed trogocytosis. In this study, we demonstrate that human Ag-specific CD8+ T cells acquire the coinhibitory molecule programmed death ligand 1 (PD-L1) from mature dendritic cells (mDC) and tumor cells in an Ag-specific manner. Immature dendritic cells were less effective in transferring surface molecules onto CD8+ T cells than mDCs. Interestingly, trogocytosis of PD-L1 requires cell–cell contact and cannot be induced by uptake of soluble proteins obtained from mDC lysates. The transfer process is impaired by inhibition of vacuolar ATPases in T cells as well as by fixation of dendritic cells. Of importance, CD8+ T cells that acquired PD-L1 complexes were able to induce apoptosis of neighboring programmed death 1–expressing CD8+ T cells. In summary, our data demonstrate that human CD8+ T cells take up functionally active PD-L1 from APCs in an Ag-specific fashion, leading to fratricide of programmed death 1–expressing, neighboring T cells. The transfer of functionally active coinhibitory molecules from APCs onto human CD8+ T cells could have a regulatory role in immune responses.

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confidence: 82%

“…Human and murine T cells exchange molecules with DCs in a bidirectional manner (12). Trogocytosis is a ubiquitous phenomenon as it is observed for T cells, DCs, B cells, NK cells, tumor cells, and other immune cells (13)(14)(15)(16)(17)(18). Moreover, trogocytosis of membrane patches was not only described in vitro, but also in vivo in mice (19).…”

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confidence: 99%

Antigen-Specific Transfer of Functional Programmed Death Ligand 1 from Human APCs onto CD8+ T Cells via Trogocytosis

Gary

Voelkl

Palmisano³

et al. 2012

The Journal of Immunology

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“…In addition to these well-known examples, other cellular structures involved in cell-cell communication have been identified (1). A frequent result of cell-cell communication is collective population behavior that can potentially lead to complex phenotypes not observed in separate individual cells, for example, in development or tumor formation (2,3). Immune responses against pathogens or any foreign antigens require fine immune regulation, where cellular communications are mediated by either soluble or cell surface molecules.…”

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confidence: 99%

Flow cytometric analyses disclose intercellular communications in FasL‐stimulated T cells: Results and trouble shooting

et al. 2011

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LIFE depends on the ability of cells to communicate with one another. Much of this crosstalk occurs at cell-cell contacts and is regulated by complex structural interface: neurological and immunological synapses that transmit cell-cell signals through the extracellular space, relying on mechanisms of ligand-receptor signalling across tight cell-cell junctions. In addition to these well-known examples, other cellular structures involved in cell-cell communication have been identified (1). A frequent result of cell-cell communication is collective population behavior that can potentially lead to complex phenotypes not observed in separate individual cells, for example, in development or tumor formation (2,3). Immune responses against pathogens or any foreign antigens require fine immune regulation, where cellular communications are mediated by either soluble or cell surface molecules. Generally, absorption, exosome production and uptake, internalization, and membrane nanotube formation are the probable mechanisms through which the membrane fragments and cytoplasmic content are transferred from one cell to another (4). The identification of new structures involved in cell-to-cell communication has led to the development of new analytical and imaging tools, which have allowed us to enhance our understanding of the ubiquitous phenomenon of cell-to-cell communication. Such tools include quantitative cell microscopy, now mainly represented by two distinct techniques: flow cytometry (FCM) and image cytometry (IC) (5). FCM allows analysis of cell suspensions, cell-by-cell quantification of optical signals, rapid analysis (several hundred cells per second), and cell sorting, whereas IC allows precise localization and quantification of optical signals emitted by each point of the observed field and image analysis (morphology and morphometry). FASL STIMULATION OF T CELLSThe Fas/CD95 surface receptor mediates rapid death of various cell types, including autoreactive T cells, which can trigger autoimmunity. In this study we investigate novel aspects of Fas signaling that define a ''social'' dimension to receptor-induced apoptosis. At least in some cell types, FasL can be stored in granules and then rapidly released at the cell surface in response to external stimuli. Alternatively, FasL can be cleaved from the membrane by matrix metalloproteases and act as a soluble cytokine (6). In its membrane-bound form, FasL acts as a ligand for Fas and can trigger Fas-induced death.In our experiments, CD41 T cells were purified from PBMC by negative selection using the MACS system. CD41 T cells and Jurkat cells were both treated with FasL at a final concentration of 0.5 lg/ml for a maximum of 2 h. Our previous findings (7) showed that Fas stimulation led to an intriguing (and previously unsuspected) asymmetry of death propagation according to cell conjugation and rapidly induced extensive membrane nanotube formation between neighboring T cells. The experiments were performed using flow cytometric (FC) and morphologic (fluorescence and ti...

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“…These ABC transporters are physiologically expressed by normal cells to maintain hermetically closed biological barriers, particularly the intestinal mucosa and the blood-brain barrier, but cancer cells are able to activate their transcription to gain protection 20 J. Clairambault Cell proliferation control and cancer treatment against anticancer agents when normal cells are not. Moreover, at least one of these transporters (the P-glycoprotein, or P-gp) may be exchanged by trogocytosis (membrane fusion) between tumour cells and special stromal cells (the so-called "hospicells"), to confer acquired resistance to these tumour cells [226]. It is a goal for pharmaceutical companies to develop ABC transporter inhibitors, that can be associated in combined treatments with the drug they are known to expel, and partial success have been obtained toward this aim by drugs such as Verapamil, Ciclosporin and others [129], some of them specific of such blockade, as Zosuquidar, that has proved activity in treated Acute Myelogenous Leukaemia (AML) [256].…”

Section: Resistance To Drugs In Cancer Cellsmentioning

confidence: 99%

Modelling Physiological and Pharmacological Control on Cell Proliferation to Optimise Cancer Treatments

Clairambault

2009

Math. Model. Nat. Phenom.

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Abstract. This review aims at presenting a synoptic, if not exhaustive, point of view on some of the problems encountered by biologists and physicians who deal with natural cell proliferation and disruptions of its physiological control in cancer disease. It also aims at suggesting how mathematicians are naturally challenged by these questions and how they might help, not only biologists to deal theoretically with biological complexity, but also physicians to optimise therapeutics, on which last point the focus will be set here. To this purpose, mathematical modelling should represent proliferating cell population dynamics with natural built-in control targets (which implies modelling the cell division cycle), together with the distribution of drugs in the organism and their molecular actions on different targets at the cell level on proliferation, i.e., molecular pharmacokinetics-pharmacodynamics of antiproliferative drugs. This should make possible optimal control of drug delivery with constraints to be determined according to the main pharmacological issues encountered in the clinic: unwanted toxic side-effects, occurrence of drug resistance. Mathematical modelling should also take into account physiological determinants of cell and tissue proliferation, such as intervention of the immune system, circadian control on cell cycle checkpoint proteins, and activity of intracellular drug processing enzymes together with individual variations in the activities of these proteins (genetic polymorphism). Taking these points into account will add to the rich scenery of normal or disrupted cell and tissue regulations, and their corrections by drugs, a natural environmental, whole body physiological, frame. It is necessary indeed to consider such a framework if one wants to eventually be actually helpful to clinicians who routinely treat by combinations of drugs living Humans with their complex whole body regulations, often dependent on genotypic variations, and not isolated cells or tissues.Key words: cell proliferation, population dynamics, physiologically structured partial differential equations, pharmacological control, pharmacokinetics-pharmacodynamics, physiological modelling, cancer treatments, therapeutic optimisation, individualised medicine AMS subject classification: 92-02, 92B05 Biological common knowledge on cancerThis section shortly presents the general scenery of cancer evolution and features that must be included in models designed to describe and control it, bearing in mind a more descriptive (physicist's) than a therapeutic (physician's) point of view, only to reverse this perspective in the following sections, in which will be stressed the interest of modelling from the point of view of control, at least if one wants to design models for therapeutic applications. This biological section will be only a short sketch, if one considers that on this subject many books have already been written, e.g. [24,78,96,97,223]. Cancer: a challenging public health problemCardiovascular diseases and cancer are by fa...

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Oncologic Trogocytosis of an Original Stromal Cells Induces Chemoresistance of Ovarian Tumours

Cited by 85 publications

References 50 publications

Antigen-Specific Transfer of Functional Programmed Death Ligand 1 from Human APCs onto CD8+ T Cells via Trogocytosis

Antigen-Specific Transfer of Functional Programmed Death Ligand 1 from Human APCs onto CD8+ T Cells via Trogocytosis

Flow cytometric analyses disclose intercellular communications in FasL‐stimulated T cells: Results and trouble shooting

Modelling Physiological and Pharmacological Control on Cell Proliferation to Optimise Cancer Treatments

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