期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 19, 期 3, 页码 -出版社
MDPI
DOI: 10.3390/ijms19030752
关键词
natural killer T cells; inflammation; cancer
资金
- Deutsche Forschungsgemeinschaft [SFB 1039 TP B04, SFB 1039 TP B06, FOR 2438]
- Deutsche Krebshilfe [70112451]
- Else Kroner Fresenius-Foundation (Graduate school Translational Research Innovation-Pharma (TRIP))
- Else Kroner Fresenius-Foundation (Else Kroner Fresenius Graduate School)
Natural Killer T cells (NKT cells) are emerging as critical regulators of pro-and anti-tumor immunity, both at baseline and in therapeutic settings. While type I NKT cells can promote anti-tumor immunity, their activity in the tumor microenvironment may be limited by negative regulators such as inhibitory immune checkpoints. We observed dominant expression of B- and T-lymphocyte attenuator (BTLA) on type I NKT cells in polyoma middle T oncogene-driven (PyMT) murine autochthonous mammary tumors. Other immune checkpoint receptors, such as programmed cell death 1 (PD-1) were equally distributed among T cell populations. Interference with BTLA using neutralizing antibodies limited tumor growth and pulmonary metastasis in the PyMT model in a therapeutic setting, correlating with an increase in type I NKT cells and expression of cytotoxic marker genes. While therapeutic application of an anti-PD-1 antibody increased the number of CD8+ cytotoxic T cells and elevated IL-12 expression, tumor control was not established. Expression of ZBTB16, the lineage-determining transcription factor of type I NKT cells, was correlated with a favorable patient prognosis in the METABRIC dataset, and BTLA levels were instrumental to further distinguish prognosis in patents with high ZBTB16 expression. Taken together, these data support a role of BTLA on type I NKT cells in limiting anti-tumor immunity.
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