Fas ligand-mediated immune surveillance by T cells is essential for the control of spontaneous B cell lymphomas
- Author(s)
- Afshar-Sterle, S; Zotos, D; Bernard, NJ; Scherger, AK; Rodling, L; Alsop, AE; Walker, J; Masson, F; Belz, GT; Corcoran, LM; O'Reilly, LA; Strasser, A; Smyth, MJ; Johnstone, R; Tarlinton, DM; Nutt, SL; Kallies, A;
- Details
- Publication Year 2014-02-02,Volume 20,Issue #3,Page 283-290
- Journal Title
- Nature medicine
- Publication Type
- Journal Article
- Abstract
- Loss of function of the tumor suppressor gene PRDM1 (also known as BLIMP1) or deregulated expression of the oncogene BCL6 occurs in a large proportion of diffuse large B cell lymphoma (DLBCL) cases. However, targeted mutation of either gene in mice leads to only slow and infrequent development of malignant lymphoma, and despite frequent mutation of BCL6 in activated B cells of healthy individuals, lymphoma development is rare. Here we show that T cells prevent the development of overt lymphoma in mice caused by Blimp1 deficiency or overexpression of Bcl6 in the B cell lineage. Impairment of T cell control results in rapid development of DLBCL-like disease, which can be eradicated by polyclonal CD8+ T cells in a T cell receptor-, CD28- and Fas ligand-dependent manner. Thus, malignant transformation of mature B cells requires mutations that impair intrinsic differentiation processes and permit escape from T cell-mediated tumor surveillance.
- Publisher
- NPG
- Research Division(s)
- Molecular Genetics Of Cancer; Immunology; Molecular Immunology
- Publisher's Version
- https://doi.org/10.1038/nm.3442
- Terms of Use/Rights Notice
- © 2014 Macmillan Publishers Limited. All Rights Reserved
Creation Date: 2014-02-18 03:39:52
Last Modified: 2015-03-26 08:02:13