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

Marcus James Robinson, Franca Ronchese, John H. Miller, Anne Camille La Flamme

Research output: Contribution to journalArticleResearchpeer-review

6 Citations (Scopus)

Abstract

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-γ 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.

Original languageEnglish
Pages (from-to)291-296
Number of pages6
JournalImmunology and Cell Biology
Volume88
Issue number3
DOIs
Publication statusPublished - Mar 2010
Externally publishedYes

Cite this

Robinson, Marcus James ; Ronchese, Franca ; Miller, John H. ; La Flamme, Anne Camille. / Paclitaxel inhibits killing by murine cytotoxic T lymphocytes in vivo but not in vitro. In: Immunology and Cell Biology. 2010 ; Vol. 88, No. 3. pp. 291-296.
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Paclitaxel inhibits killing by murine cytotoxic T lymphocytes in vivo but not in vitro. / Robinson, Marcus James; Ronchese, Franca; Miller, John H.; La Flamme, Anne Camille.

In: Immunology and Cell Biology, Vol. 88, No. 3, 03.2010, p. 291-296.

Research output: Contribution to journalArticleResearchpeer-review

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