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Cytotoxic T lymphoc...
Cytotoxic T lymphocytes induce caspase-dependent and -independent cell death in neuroblastomas in a MHC-nonrestricted fashion
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De Geer, A (författare)
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- Kiessling, R (författare)
- Karolinska Institutet
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- Levitsky, V (författare)
- Karolinska Institutet
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Levitskaya, J (författare)
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(creator_code:org_t)
- The American Association of Immunologists, 2006
- 2006
- Engelska.
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Ingår i: Journal of immunology (Baltimore, Md. : 1950). - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 177:11, s. 7540-7550
- Relaterad länk:
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http://www.jimmunol....
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http://kipublication...
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https://doi.org/10.4...
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Abstract
Ämnesord
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- The MHC class I- restricted processing and presentation pathway is frequently nonfunctional in tumor cells; therefore, the direct targeting of tumor cells by CTLs may be difficult, if at all possible, to achieve. We used neuroblastoma (NB), which represents a striking example of a tumor with an impaired MHC class I pathway, as a model to study bystander effects of activated T lymphocytes on tumor cells. We found that NB cell lines are susceptible to killing by differentiated CD8+ CTL clones in a MHC class I-nonrestricted manner that involves two programs of cell death distinguished on the basis of different kinetics, sensitivities to caspase inhibitors, and cytokine-blocking reagents. The “early” death exhibited characteristic features of apoptosis, whereas the “delayed” caspase-independent death exhibited features associated with necrosis and was partially inhibited by TNF-α-blocking and prevented by overexpression of Bcl-2 or Bcl-xL. Our data reveal a previously unappreciated complexity of death pathways induced in tumor cells by immune activation and suggest that redirecting nonspecific effector CTLs to even a small proportion of NB cells or activating CTLs in a tumor’s proximity may have therapeutic effects in patients with NB.
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