TY  - JOUR
A1  - Sekar, Divya
A1  - Govene, Luisa
A1  - Río, María-Luisa del
A1  - Sirait-Fischer, Evelyn Nicole Joy
A1  - Fink, Annika F.
A1  - Brüne, Bernhard
A1  - Rodriguez-Barbosa, José I.
A1  - Weigert, Andreas
T1  - Downregulation of BTLA on NKT cells promotes tumor immune control in a mouse model of mammary carcinoma
T2  - International journal of molecular sciences
N2  - 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.
KW  - cancer
KW  - inflammation
KW  - natural killer T cells
Y1  - 2018
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/45798
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-457983
SN  - 1422-0067
SN  - 1661-6596
N1  - This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
VL  - 19
IS  - 3, Art. 752
SP  - 1
EP  - 12
PB  - Molecular Diversity Preservation International
CY  - Basel
ER  -