TY  - JOUR
AU  - Raute, Katrin
AU  - Strietz, Juliane
AU  - Parigiani, Maria Alejandra
AU  - Andrieux, Geoffroy
AU  - Thomas, Oliver S
AU  - Kistner, Klaus M
AU  - Zintchenko, Marina
AU  - Aichele, Peter
AU  - Hofmann, Maike
AU  - Zhou, Houjiang
AU  - Weber, Wilfried
AU  - Börries, Melanie
AU  - Swamy, Mahima
AU  - Maurer, Jochen
AU  - Minguet, Susana
TI  - Breast Cancer Stem Cell-Derived Tumors Escape from γδ T-cell Immunosurveillance In Vivo by Modulating γδ T-cell Ligands.
JO  - Cancer immunology research
VL  - 11
IS  - 6
SN  - 2326-6066
CY  - Philadelphia, Pa.
PB  - AACR
M1  - DKFZ-2023-00875
SP  - 810-829
PY  - 2023
N1  - 2023 Jun 2;11(6):810-829
AB  - There are no targeted therapies for patients with triple-negative breast cancer (TNBC). TNBC is enriched in breast cancer stem cells (BCSC), which play a key role in metastasis, chemoresistance, relapse, and mortality. γδ T cells hold great potential in immunotherapy against cancer and might provide an approach to therapeutically target TNBC. γδ T cells are commonly observed to infiltrate solid tumors and have an extensive repertoire of tumor-sensing mechanisms, recognizing stress-induced molecules and phosphoantigens (pAgs) on transformed cells. Herein, we show that patient-derived triple-negative BCSCs are efficiently recognized and killed by ex vivo expanded γδ T cells from healthy donors. Orthotopically xenografted BCSCs, however, were refractory to γδ T-cell immunotherapy. We unraveled concerted differentiation and immune escape mechanisms: xenografted BCSCs lost stemness, expression of γδ T-cell ligands, adhesion molecules, and pAgs, thereby evading immune recognition by γδ T cells. Indeed, neither promigratory engineered γδ T cells, nor anti-PD-1 checkpoint blockade, significantly prolonged overall survival of tumor-bearing mice. BCSC immune escape was independent of the immune pressure exerted by the γδ T cells and could be pharmacologically reverted by zoledronate or IFNα treatment. These results pave the way for novel combinatorial immunotherapies for TNBC.
LB  - PUB:(DE-HGF)16
C6  - pmid:37139603
DO  - DOI:10.1158/2326-6066.CIR-22-0296
UR  - https://inrepo02.dkfz.de/record/275781
ER  -