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Cancer Immunol Res. 2017 Nov;5(11):1016-1028. doi: 10.1158/2326-6066.CIR-17-0056. Epub 2017 Sep 18.

Immunosurveillance and Immunoediting of Breast Cancer via Class I MHC Receptors.

Author information

1
Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Canada.
2
Department of Microbiology and Immunology, Dalhousie University, Halifax, Canada.
3
College of Applied Medical Sciences, Taibah University, Madinah Munawwarah, Saudi Arabia.
4
Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Canada. amakrigiannis@dal.ca.

Abstract

Ly49 receptors, which recognize "self" class I major histocompatibility complex (MHC-I) molecules, enable natural killer (NK) cells to detect loss of MHC-I expression on transformed and virally infected cells. The impact of NK cell-mediated MHC-I surveillance on immunoediting of breast cancer is still not fully understood. This work assesses the impact of Ly49 receptors on tumor development in terms of cancer control and in driving immune-evading cancer mutations. Genetically modified Ly49-deficient mice and those lacking NK cells through antibody depletion were less able to control E0771-derived mammary tumors in an MHC-I-dependent fashion. Similarly, Ly49-deficient MMTV-PyVT-transgenic mice developed spontaneous mammary tumors faster than Ly49-sufficient MMTV-PyVT mice. Fewer CD69+ and granzyme B+ NK cells were detected among the tumor-infiltrating lymphocytes in Ly49-deficient than in Ly49-sufficient MMTV-PyVT mice. Furthermore, tumors from Ly49-deficient mice displayed reduced MHC-I expression, suggesting that tumors growing in these mice lacked an Ly49-derived pressure to maintain MHC-I expression. These same MHC-I-low tumors from Ly49-deficient mice were unable to flourish when transferred to Ly49-sufficient hosts, confirming that this tumor mutation was in response to an Ly49-deficient environment. This work demonstrates a role for Ly49 receptors in the control of mammary cancer, and provides evidence to support a model of tumor immunoediting, in which selective pressures from the immune system drive immune-evasive cancer mutations. Cancer Immunol Res; 5(11); 1016-28. ©2017 AACR.

PMID:
28924054
DOI:
10.1158/2326-6066.CIR-17-0056
[Indexed for MEDLINE]
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