Cancer Immunoediting of the NK Group 2D Ligand H60a

The Journal of Immunology: Official Journal of the American Association of Immunologists

Gavin P. Dunn¹  Robert D. Schreiber²  Daphne Y. Lacoursiere³  Timothy O’Sullivan⁴  Jack D. Bui⁵ 

[1]and

[2]Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110

[3]Department of Pathology, University of California at San Diego, La Jolla, CA 92093

[4]Department of Reproductive Medicine, University of California at San Diego, La Jolla, CA 92093

DOI  :  10.4049/jimmunol.1100413

学科分类：生物科学（综合）

来源: American Association of Immunologists

【 摘 要 】

Cancer immunoediting describes the process whereby highly immunogenic tumor cells are removed, or edited, from the primary tumor repertoire by the immune system. In immunodeficient mice, the editing process is hampered, and “unedited” tumor cells can be recovered and studied. In this study, we compared unedited and edited tumors for their expression of NK group 2D (NKG2D) ligands, a family of surface proteins expressed on tumor cells that can activate NK cell cytotoxic activity. We found that the expression of the NKG2D ligand H60a was more heterogeneous in groups of unedited 3′-methylcholanthrene sarcoma cell lines compared with that in edited 3′-methylcholanthrene sarcoma cell lines (i.e., some unedited cell lines expressed very high levels of H60a, whereas other unedited and edited cell lines expressed very low levels). We also found that some highly immunogenic cell lines displayed a bimodal distribution consisting of H60a-hi and H60a-lo cells. In one of these cell lines, the H60a-hi cells could be removed by passaging the cells through RAG2−/− mice, resulting in edited cell lines that were poor targets for NK cells and that displayed progressive tumor growth. This editing of H60a-hi cells required NK cells and NKG2D. Our studies show that the expression of H60a on tumors cells can be actively modulated by the immune system, thereby implicating this NKG2D ligand in tumor immunosurveillance.

【 授权许可】

CC BY