Fas ligand-mediated immune surveillance by T cells is essential for the control of spontaneous B cell lymphomas

Shoukat Afshar-Sterle, Dimitra Zotos, Nicholas J. Bernard, Anna K. Scherger, Lisa Rödling, Amber E. Alsop, Jennifer A Walker, Frederick Masson, Gabrielle T Belz, Lynn M. Corcoran, Lorraine A O'Reilly, Andreas Strasser, Mark J. Smyth, Ricky Johnstone, David M. Tarlinton, Stephen L Nutt, Axel Kallies

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53 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)283-290
Number of pages8
JournalNature Medicine
Volume20
Issue number3
DOIs
Publication statusPublished - 2014
Externally publishedYes

Cite this

Afshar-Sterle, S., Zotos, D., Bernard, N. J., Scherger, A. K., Rödling, L., Alsop, A. E., Walker, J. A., Masson, F., Belz, G. T., Corcoran, L. M., O'Reilly, L. A., Strasser, A., Smyth, M. J., Johnstone, R., Tarlinton, D. M., Nutt, S. L., & Kallies, A. (2014). Fas ligand-mediated immune surveillance by T cells is essential for the control of spontaneous B cell lymphomas. Nature Medicine, 20(3), 283-290. https://doi.org/10.1038/nm.3442