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Human breast tumor cells induce self-tolerance mechanisms to avoid NKG2D-mediated and DNAM-mediated NK cell recognition.
- Source :
-
Cancer research [Cancer Res] 2011 Nov 01; Vol. 71 (21), pp. 6621-32. Date of Electronic Publication: 2011 Sep 21. - Publication Year :
- 2011
-
Abstract
- Breast cancer is the leading cause of death for women between the ages of 35 to 65. This is mostly due to intertumor heterogeneity and the lack of specific therapies for all subtypes. However, some breast cancers with an unexpected good prognosis are associated with enhanced antitumor immunity in situ. We studied whether breast cancer subtypes might have different susceptibilities to natural killer (NK) cells' antitumor immunity. We collected a large public set of microarray data for primary breast tumors and determined NK cell ligand expression. We found that despite heterogeneous levels of inhibitory HLA members, NKG2D ligands and DNAM ligands are expressed in virtually all breast tumor subtypes. Functional experiments in breast cancer subtypes expressing various levels of NK cell ligands showed that NK-mediated cytotoxicity is mainly HLA, NKG2D, and DNAM dependent. In parallel, we showed that cell lines and primary breast tumor cells secrete soluble inhibitory factors that alter NK cell functions. Finally, we showed that these mechanisms of escape occur in vivo in the MMTV-Neu model of spontaneous murine breast cancer. Our study shows that breast cancer cells, independent of the subtype, have developed different mechanisms to escape from NK cells' antitumor immunity. These results emphasize the role of NK cells in breast tumor clearance and underlie the importance of devising future therapy aiming at enhancing NK cell-mediated recognition in parallel with the prevention of the tumor-editing process.<br /> (©2011 AACR.)
- Subjects :
- Animals
Breast Neoplasms classification
Breast Neoplasms genetics
Breast Neoplasms pathology
Carcinoma, Ductal, Breast classification
Carcinoma, Ductal, Breast genetics
Carcinoma, Ductal, Breast pathology
Cell Line, Tumor immunology
Cell Line, Tumor metabolism
Cytotoxicity, Immunologic
Estrogens
Female
Gene Expression Profiling
Humans
Killer Cells, Natural classification
Ligands
Mammary Neoplasms, Experimental genetics
Mammary Neoplasms, Experimental immunology
Mice
Neoplasm Proteins biosynthesis
Neoplasm Proteins genetics
Neoplasms, Hormone-Dependent genetics
Neoplasms, Hormone-Dependent immunology
Neoplasms, Hormone-Dependent pathology
Progesterone
RNA, Messenger biosynthesis
RNA, Messenger genetics
RNA, Neoplasm biosynthesis
RNA, Neoplasm genetics
Receptors, Immunologic immunology
Antigens, Differentiation, T-Lymphocyte immunology
Breast Neoplasms immunology
Carcinoma, Ductal, Breast immunology
Killer Cells, Natural immunology
NK Cell Lectin-Like Receptor Subfamily K immunology
Self Tolerance
Tumor Escape
Subjects
Details
- Language :
- English
- ISSN :
- 1538-7445
- Volume :
- 71
- Issue :
- 21
- Database :
- MEDLINE
- Journal :
- Cancer research
- Publication Type :
- Academic Journal
- Accession number :
- 21937679
- Full Text :
- https://doi.org/10.1158/0008-5472.CAN-11-0792