Metastatic Consequences of Immune Escape from NK Cell Cytotoxicity by Human Breast Cancer Stem Cells
Open Access
- 14 October 2014
- journal article
- Published by American Association for Cancer Research (AACR) in Cancer Research
- Vol. 74 (20), 5746-5757
- https://doi.org/10.1158/0008-5472.can-13-2563
Abstract
Breast cancer stem-like cells (BCSC) are crucial for metastasis but the underlying mechanisms remain elusive. Here, we report that tumor-infiltrating natural killer (NK) cells failed to limit metastasis and were not associated with improved therapeutic outcome of BCSC-rich breast cancer. Primary BCSCs were resistant to cytotoxicity mediated by autologous/allogeneic NK cells due to reduced expression of MICA and MICB, two ligands for the stimulatory NK cell receptor NKG2D. Furthermore, the downregulation of MICA/MICB in BCSCs was mediated by aberrantly expressed oncogenic miR20a, which promoted the resistance of BCSC to NK cell cytotoxicity and resultant lung metastasis. The breast cancer cell differentiation–inducing agent, all-trans retinoic acid, restored the miR20a–MICA/MICB axis and sensitized BCSC to NK cell–mediated killing, thereby reducing immune escape–associated BCSC metastasis. Together, our findings reveal a novel mechanism for immune escape of human BCSC and identify the miR20a–MICA/MICB signaling axis as a therapeutic target to limit metastatic breast cancer. Cancer Res; 74(20); 5746–57. ©2014 AACR.Keywords
Other Versions
This publication has 48 references indexed in Scilit:
- Epithelial-to-Mesenchymal Transition and Autophagy Induction in Breast Carcinoma Promote Escape from T-cell–Mediated LysisCancer Research, 2013
- Cytotoxic T cells induce proliferation of chronic myeloid leukemia stem cells by secreting interferon-γThe Journal of Experimental Medicine, 2013
- Nanog signaling in cancer promotes stem-like phenotype and immune evasionJCI Insight, 2012
- The evolving concept of cancer and metastasis stem cellsThe Journal of cell biology, 2012
- Silencing of Irf7 pathways in breast cancer cells promotes bone metastasis through immune escapeNature Medicine, 2012
- Cancer Stem Cells: Current Status and Evolving ComplexitiesCell Stem Cell, 2012
- Cancer Vaccination Drives Nanog-Dependent Evolution of Tumor Cells toward an Immune-Resistant and Stem-like PhenotypeCancer Research, 2012
- Concise Review: Contribution of Cancer Stem Cells to NeovascularizationThe International Journal of Cell Cloning, 2011
- Cancer Immunoediting: Integrating Immunity’s Roles in Cancer Suppression and PromotionScience, 2011
- Immune-Induced Epithelial to Mesenchymal Transition In vivo Generates Breast Cancer Stem CellsCancer Research, 2009