Downregulation of BTLA on NKT Cells Promotes Tumor Immune Control in a Mouse Model of Mammary Carcinoma
AbstractNatural 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. View Full-Text
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Sekar, D.; Govene, L.; del Río, M.-L.; Sirait-Fischer, E.; Fink, A.F.; Brüne, B.; Rodriguez-Barbosa, J.I.; Weigert, A. Downregulation of BTLA on NKT Cells Promotes Tumor Immune Control in a Mouse Model of Mammary Carcinoma. Int. J. Mol. Sci. 2018, 19, 752.
Sekar D, Govene L, del Río M-L, Sirait-Fischer E, Fink AF, Brüne B, Rodriguez-Barbosa JI, Weigert A. Downregulation of BTLA on NKT Cells Promotes Tumor Immune Control in a Mouse Model of Mammary Carcinoma. International Journal of Molecular Sciences. 2018; 19(3):752.Chicago/Turabian Style
Sekar, Divya; Govene, Luisa; del Río, María-Luisa; Sirait-Fischer, Evelyn; Fink, Annika F.; Brüne, Bernhard; Rodriguez-Barbosa, José I.; Weigert, Andreas. 2018. "Downregulation of BTLA on NKT Cells Promotes Tumor Immune Control in a Mouse Model of Mammary Carcinoma." Int. J. Mol. Sci. 19, no. 3: 752.
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