Exposure to paclitaxel or vinblastine down-regulates CD11a and CD54 expression by P815 mastocytoma cells and renders the tumor cells resistant to killing by nonspecific cytotoxic T lymphocytes induced with anti-CD3 antibody

ChuanLi, Zhao; Morgan, Max; Haeryfar, S.M. Mansour; Blay, Jonathan

doi:10.1007/s00262-002-0357-4

Cited by 8 publications

(3 citation statements)

References 37 publications

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“…Paclitaxel has been shown previously to ablate leukocyte infiltration into the peritoneum after lipopolysaccharide administration, 27 to inhibit the ability of human CTLs to recycle and kill multiple targets in vitro, 28 and to reduce TC expression of molecules involved in stabilising of the immunological synapse in vitro. 29 If taxane therapy alters the tissue homing of CTLs, increases the time for which an individual CTL synapses with a TC, or limits the ability of CTLs to recognise TCs, all would plausibly explain the reduced killing seen in vivo but not in vitro. Although we see it as most likely that CTL recycling is diminished in vivo as seen for human CTL in vitro, 28 further study will be required to define how MSDs alter murine CTL function in vivo and to model these effects in vitro.…”

Section: Discussionmentioning

confidence: 99%

“…As CTL‐mediated killing is contact dependent, CTLs must encounter TCs to induce specific apoptosis. Paclitaxel has been shown previously to ablate leukocyte infiltration into the peritoneum after lipopolysaccharide administration, 27 to inhibit the ability of human CTLs to recycle and kill multiple targets in vitro , 28 and to reduce TC expression of molecules involved in stabilising of the immunological synapse in vitro 29 . If taxane therapy alters the tissue homing of CTLs, increases the time for which an individual CTL synapses with a TC, or limits the ability of CTLs to recognise TCs, all would plausibly explain the reduced killing seen in vivo but not in vitro .…”

Section: Discussionmentioning

confidence: 99%

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Paclitaxel inhibits killing by murine cytotoxic T lymphocytes in vivo but not in vitro

et al. 2009

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To kill antigen-specific target cells (TCs), cytotoxic T lymphocytes (CTLs) reorganise their microtubule cytoskeleton to deliver lytic granules to the TCs. We used two drugs that stabilise microtubules, paclitaxel and peloruside, to determine how the stabilising microtubule network affects CTL function in vitro and in vivo. In vitro, neither paclitaxel nor peloruside inhibited antigen-specific killing, lytic granule delivery to the cell surface, nor interferon-c release by murine CTLs. In contrast, in an in vivo murine model of antigen-induced killing, a single dose of paclitaxel had a significant inhibitory effect on killing by CTLs. Furthermore, the inhibitory effect of paclitaxel was not caused by specific deletion of the effector CTL population in drug-treated mice. The findings reveal that microtubule-stabilising drug treatment can lead to immediate impairment of CTL function without affecting lytic granule release. The results also suggest that patients undergoing taxane anti-cancer therapy may be impaired in their ability to fight infection before the anti-mitotic effects of paclitaxel are apparent.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Paclitaxel inhibits killing by murine cytotoxic T lymphocytes in vivo but not in vitro

et al. 2009

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“…In support of this, pre-treatment of murine cell lines with paclitaxel reduces surface expression of CD11a and CD54 (Zhao et al, 2003), both of which are involved in stabilisation of the IS (Monks et al, 1998;Stinchcombe et al, 2001b;Stinchcombe and Griffiths, 2003;Stinchcombe et al, 2006). This decreased expression directly correlates with reduced lysis of the cells by CD3-activated lymphocytes (Zhao et al, 2003). If such modifications have an effect in vivo, cytolysis will be inhibited.…”

Section: Discussionmentioning

confidence: 87%

The Effect of Microtubule Stabilising Drugs on Immune-Mediated Excytosis

Robinson¹

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<p>The microtubule network is involved in cellular processes including protein transport and cell division. Microtubule stabilising drugs (MSD) bind to microtubules and alter their dynamic balance in favour of the polymerised state. While primarily known for their anti-mitotic properties, MSD also exert immunomodulatory effects in vitro and in vivo. It is the aim of this project to investigate the effects of MSD on protein trafficking and secretion to determine how they affect immune-mediated exocytosis. Previous work in our lab demonstrated that macrophage responses to bacterial lipopolysaccharide, as measured by the production of TNF-a and nitric oxide, are inhibited by both paclitaxel and peloruside. In this thesis we continued this work and saw that inhibition was not affected by temporal IFN-y priming and found that altered production kinetics were not sufficient to explain the inhibition. To kill target cells cytotoxic T cells (CTL) reorganise their cytoskeleton so that lytic granules can traffic down microtubules to be delivered to the target. Using an in vitro model of CTL killing, we saw that MSD did not inhibit killing by CTL, lytic granule delivery to the cell surface, or antigen-stimulated Interferon-y (IFN-y) production by CTL. In contrast to this, in a murine model of antigen-induced killing we saw that a single dose of paclitaxel had a significant inhibitory effect on CTL-mediated cytolysis in vivo. Together these studies suggest that MSD have multiple immunomodulatory effects that are independent of their anti-proliferative effects. The data suggest that patients undergoing taxane therapy may be unable to fight infection long before the anti-mitotic effects of MSD are apparent.</p>

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Reduced potency of cytotoxic T lymphocytes from patients with high-risk myelodysplastic syndromes

Sand

Theorell

Bruserud

et al. 2016

Cancer Immunol Immunother

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Exposure to paclitaxel or vinblastine down-regulates CD11a and CD54 expression by P815 mastocytoma cells and renders the tumor cells resistant to killing by nonspecific cytotoxic T lymphocytes induced with anti-CD3 antibody

Cited by 8 publications

References 37 publications

Paclitaxel inhibits killing by murine cytotoxic T lymphocytes in vivo but not in vitro

Paclitaxel inhibits killing by murine cytotoxic T lymphocytes in vivo but not in vitro

The Effect of Microtubule Stabilising Drugs on Immune-Mediated Excytosis

Reduced potency of cytotoxic T lymphocytes from patients with high-risk myelodysplastic syndromes

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