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.

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Figures

Figure 1

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

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.

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