DOI: 10.4049/jimmunol.167.4.2068. A Central Role for Death Receptor-Mediated Apoptosis in the Rejection of Tumors by NK Cells

A Central Role for Death Receptor-Mediated Apoptosis in the Rejection of Tumors by NK Cells

10.4049/jimmunol.167.4.2068

Crossref journal-article

Oxford University Press (OUP)

The Journal of Immunology (286)

Abstract

AbstractNK cells provide a line of defense against tumors and virus-infected cells that have lost the expression of one or more MHC class I isoforms. Here, we investigate whether inhibitors of apoptosis can block the rejection of tumors mediated by NK cells, by introducing the long form of Fas-associated death domain-like IL-1β-converting enzyme-associated inhibitory protein (FLIPL) and poxvirus cytokine response modifier A (CrmA) into the MHC class I-deficient T lymphoma cell line RMA-S. RMA-S cells do not normally express Fas in vitro, and it was previously postulated that the rejection of these tumors by NK cells is strictly perforin dependent. We show that perforin-deficient NK cells directly mediate Fas up-regulation on RMA-S cells and thereafter kill the cells in a Fas-dependent manner, and that RMA-S FLIPL and RMA-S CrmA are protected from such killing. When injected in immunocompetent recipients, RMA-S cells up-regulate Fas, rendering in vivo-passed mock-transduced cells sensitive to Fas-mediated apoptosis. Moreover, RMA-S FLIPL and RMA-S CrmA cells establish aggressive tumors, in contrast to RMA-S mock cells that are rejected. These results demonstrate that FLIPL and CrmA function as tumor progression factors by protecting MHC class I-deficient tumors from rejection mediated by NK cells. Moreover, our data indicate that death receptor-mediated apoptosis has a more prominent role in the clearance of NK-sensitive tumors than previously suggested.

Bibliography

Screpanti, V., Wallin, R. P. A., Ljunggren, H.-G., & Grandien, A. (2001). A Central Role for Death Receptor-Mediated Apoptosis in the Rejection of Tumors by NK Cells. The Journal of Immunology, 167(4), 2068â2073.

Authors 4

Valentina Screpanti (first)
Robert P. A. Wallin (additional)
Hans-Gustaf Ljunggren (additional)
Alf Grandien (additional)

References 31 Referenced 151

Dates

Type	When
Created	11 years, 4 months ago (April 22, 2014, 7:18 p.m.)
Deposited	7 months, 3 weeks ago (Jan. 2, 2025, 2 p.m.)
Indexed	1 month, 1 week ago (July 12, 2025, 6:56 p.m.)
Issued	24 years ago (Aug. 15, 2001)
Published	24 years ago (Aug. 15, 2001)
Published Print	24 years ago (Aug. 15, 2001)

Funders 0

None

BibTeX

@article{Screpanti_2001, title={A Central Role for Death Receptor-Mediated Apoptosis in the Rejection of Tumors by NK Cells}, volume={167}, ISSN={1550-6606}, url={http://dx.doi.org/10.4049/jimmunol.167.4.2068}, DOI={10.4049/jimmunol.167.4.2068}, number={4}, journal={The Journal of Immunology}, publisher={Oxford University Press (OUP)}, author={Screpanti, Valentina and Wallin, Robert P. A. and Ljunggren, Hans-Gustaf and Grandien, Alf}, year={2001}, month=aug, pages={2068–2073} }

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