Influence of natural killer cells and perforin-mediated cytolysis on the development of chemically induced lung cancer in A/J mice

Frese-Schaper, Manuela; Keil, Andreas; Yagita, Hideo; Steiner, Selina; Falk, Werner; Schmid, Ralph; Frese, Steffen R. (2014). Influence of natural killer cells and perforin-mediated cytolysis on the development of chemically induced lung cancer in A/J mice. Cancer immunology, immunotherapy, 63(6), pp. 571-580. Springer 10.1007/s00262-014-1535-x

[img] Text
art%3A10.1007%2Fs00262-014-1535-x.pdf - Published Version
Restricted to registered users only
Available under License Publisher holds Copyright.

Download (1MB) | Request a copy

One alternative approach for the treatment of lung cancer might be the activation of the immune system using vaccination strategies. However, most of clinical vaccination trials for lung cancer did not reach their primary end points, suggesting that lung cancer is of low immunogenicity. To provide additional experimental information about this important issue, we investigated which type of immune cells contributes to the protection from lung cancer development. Therefore, A/J mice induced for lung adenomas/adenocarcinomas by the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) were depleted of CD4(+) or CD8(+) T cells, CD11b(+) macrophages, Gr-1(+) neutrophils and asialo GM1(+) natural killer (NK) cells. Subsequent analysis of tumour growth showed an increase in tumour number only in mice depleted of NK cells. Further asking by which mechanism NK cells suppressed tumour development, we neutralized several death ligands of the tumour necrosis factor (TNF) family known to be involved in NK cell-mediated cytotoxicity. However, neither depletion of TNF-α, TNF-related apoptosis-inducing ligand, TNF-like weak inducer of apoptosis or FasL alone nor in combination induced an augmentation of tumour burden. To show whether an alternative cell death pathway is involved, we next generated A/J mice deficient for perforin. After challenging with NNK, mice deficient for perforin showed an increase in tumour number and volume compared to wild-type A/J mice. In summary, our data suggest that NK cells and perforin-mediated cytolysis are critically involved in the protection from lung cancer giving promise for further immunotherapeutic strategies for this disease.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Thoracic Surgery
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Mu50 > Forschungsgruppe Thoraxchirurgie

UniBE Contributor:

Frese-Schaper, Manuela; Keil, Andreas; Steiner, Selina; Schmid, Ralph and Frese, Steffen R.

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0340-7004

Publisher:

Springer

Language:

English

Submitter:

Thomas Michael Marti

Date Deposited:

16 Mar 2015 13:23

Last Modified:

11 Jul 2017 13:10

Publisher DOI:

10.1007/s00262-014-1535-x

PubMed ID:

24658838

BORIS DOI:

10.7892/boris.53743

URI:

https://boris.unibe.ch/id/eprint/53743

Actions (login required)

Edit item Edit item
Provide Feedback