Type I natural killer T cells suppress tumors caused by p53 loss in mice - PubMed (original) (raw)
Type I natural killer T cells suppress tumors caused by p53 loss in mice
Jeremy B Swann et al. Blood. 2009.
Abstract
CD1d-restricted T cells are considered to play a host protective effect in tumor immunity, yet the evidence for a role of natural killer T (NKT) cells in tumor immune surveillance has been weak and data from several tumor models has suggested that some (type II) CD1d-restricted T cells may also suppress some types of antitumor immune response. To substantiate an important role for CD1d-restricted T cells in host response to cancer, we have evaluated tumor development in p53(+/-) mice lacking either type I NKT cells (TCR Jalpha18(-/-)) or all CD1d-restricted T cells (CD1d(-/-)). Our findings support a key role for type I NKT cells in suppressing the onset of sarcomas and hematopoietic cancers caused by p53 loss but do not suggest that other CD1d-restricted T cells are critical in regulating the same tumor development.
Figures
Figure 1
Tumor onset is accelerated in p53+/− mice lacking CD1d-restricted NKT cells. (A) Groups of p53+/− (C57BL/6 WT, CD1d−/−, and Jα18−/−) mice were aged, and the incidence of tumors (verified by histology as the proportion of the whole starting cohort with tumor) was determined after 750 days. (*P < .05; **P < .01; ns, not significant, using a Fisher exact test compared with B6 p53+/− control mice.) Survival curves depict the survival of p53+/− BL/6, p53+/−CD1d−/−, and p53+/−Jα18−/− mice (excluding the small number of those dying of unknown causes) monitored for 750 days (B). Panels (C: female) and (D: male) show survival curves of the same mice, divided on the basis of sex. Data are presented as percentage of survival over time. (*P < .05; ***P < .001, using a log-rank test compared with B6 p53+/− control mice.) The age at death of tumor burdened total (E), female (F), and male (G) mice is represented in scatterplots showing mean plus or minus SEM. Cohort sample sizes: n = 139 B6 p53+/− mice (n = 60 female and n = 79 male), n = 39 p53+/−Jα18−/− mice (n = 22 female and n = 17 male), n = 61 p53+/−CD1d−/− mice (n = 36 female and n = 25 male). (*P < .05; ***P < .001 using a Kruskal-Wallis test compared with B6 p53+/− control mice.)
Figure 2
Tumor spectrum in p53+/− mice lacking CD1d-restricted NKT cells. Tumor sections were analyzed by a trained pathologist in a blinded manner, and tumors were classified into 5 basic categories based on morphologic appearance: osteosarcomas, spindle cell tumors, and other sarcomas (SCT & other sarc), carcinomas and adenocarcinomas [(adeno)carcinoma], hematopoietic, and other malignancies are shown. Data are shown for all tumor burdened mice in various p53+/− strains, C57BL/6, Jα18−/−, and CD1d−/−, regardless of sex (A), and cohorts are further subdivided into both female (B) and male (C) cases.
Comment in
- NKT cells in p53 deficiency.
Dhodapkar MV, Neparidze N. Dhodapkar MV, et al. Blood. 2009 Jun 18;113(25):6268-9. doi: 10.1182/blood-2009-03-211318. Blood. 2009. PMID: 19541831 No abstract available.
Similar articles
- Defining a novel subset of CD1d-dependent type II natural killer T cells using natural killer cell-associated markers.
Singh AK, Rhost S, Löfbom L, Cardell SL. Singh AK, et al. Scand J Immunol. 2019 Sep;90(3):e12794. doi: 10.1111/sji.12794. Epub 2019 Jun 26. Scand J Immunol. 2019. PMID: 31141185 Free PMC article. - Human invariant V alpha 24-J alpha Q TCR supports the development of CD1d-dependent NK1.1+ and NK1.1- T cells in transgenic mice.
Capone M, Cantarella D, Schümann J, Naidenko OV, Garavaglia C, Beermann F, Kronenberg M, Dellabona P, MacDonald HR, Casorati G. Capone M, et al. J Immunol. 2003 Mar 1;170(5):2390-8. doi: 10.4049/jimmunol.170.5.2390. J Immunol. 2003. PMID: 12594262 - Crosstalk between type II NKT cells and T cells leads to spontaneous chronic inflammatory liver disease.
Weng X, He Y, Visvabharathy L, Liao CM, Tan X, Balakumar A, Wang CR. Weng X, et al. J Hepatol. 2017 Oct;67(4):791-800. doi: 10.1016/j.jhep.2017.05.024. Epub 2017 Jul 14. J Hepatol. 2017. PMID: 28596110 Free PMC article. - The Role of Adaptor Proteins in the Biology of Natural Killer T (NKT) Cells.
Gerth E, Mattner J. Gerth E, et al. Front Immunol. 2019 Jun 25;10:1449. doi: 10.3389/fimmu.2019.01449. eCollection 2019. Front Immunol. 2019. PMID: 31293596 Free PMC article. Review. - Immunotherapeutic strategies targeting natural killer T cell responses in cancer.
Shissler SC, Bollino DR, Tiper IV, Bates JP, Derakhshandeh R, Webb TJ. Shissler SC, et al. Immunogenetics. 2016 Aug;68(8):623-38. doi: 10.1007/s00251-016-0928-8. Epub 2016 Jul 8. Immunogenetics. 2016. PMID: 27393665 Free PMC article. Review.
Cited by
- Intratumoral NKT cell accumulation promotes antitumor immunity in pancreatic cancer.
Li J, Moresco P, Fearon DT. Li J, et al. Proc Natl Acad Sci U S A. 2024 Jul 16;121(29):e2403917121. doi: 10.1073/pnas.2403917121. Epub 2024 Jul 9. Proc Natl Acad Sci U S A. 2024. PMID: 38980903 Free PMC article. - T Cell Receptor-Engaging Monoclonal Antibodies Mobilize the Anti-Tumor Functions of Invariant Natural Killer T Cells.
Das R. Das R. Crit Rev Oncog. 2024;29(1):69-81. doi: 10.1615/CritRevOncog.2023049947. Crit Rev Oncog. 2024. PMID: 38421715 - Dysfunctional states of unconventional T-cell subsets in cancer.
Katsnelson EN, Spengler A, Domenico J, Couts KL, Loh L, Gapin L, McCarter MD, Tobin RP. Katsnelson EN, et al. J Leukoc Biol. 2024 Jan 5;115(1):36-46. doi: 10.1093/jleuko/qiad129. J Leukoc Biol. 2024. PMID: 37837379 Free PMC article. - Adoptive Immunotherapy With Engineered iNKT Cells to Target Cancer Cells and the Suppressive Microenvironment.
Delfanti G, Dellabona P, Casorati G, Fedeli M. Delfanti G, et al. Front Med (Lausanne). 2022 May 9;9:897750. doi: 10.3389/fmed.2022.897750. eCollection 2022. Front Med (Lausanne). 2022. PMID: 35615083 Free PMC article. Review. - Natural killer T cell immunotherapy combined with IL-15-expressing oncolytic virotherapy and PD-1 blockade mediates pancreatic tumor regression.
Nelson A, Gebremeskel S, Lichty BD, Johnston B. Nelson A, et al. J Immunother Cancer. 2022 Mar;10(3):e003923. doi: 10.1136/jitc-2021-003923. J Immunother Cancer. 2022. PMID: 35246474 Free PMC article.
References
- Swann JB, Coquet JM, Smyth MJ, Godfrey DI. CD1-restricted T cells and tumor immunity. Curr Top Microbiol Immunol. 2007;314:293–323. - PubMed
- Godfrey DI, MacDonald HR, Kronenberg M, Smyth MJ, Van Kaer L. NKT cells: what's in a name? Nat Rev Immunol. 2004;4:231–237. - PubMed
- Hayakawa Y, Godfrey DI, Smyth MJ. Alpha-galactosylceramide: potential immunomodulatory activity and future application. Curr Med Chem. 2004;11:241–252. - PubMed
- Terabe M, Matsui S, Noben-Trauth N, et al. NKT cell-mediated repression of tumor immunosurveillance by IL-13 and the IL-4R-STAT6 pathway. Nat Immunol. 2000;1:515–520. - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Research Materials
Miscellaneous