Regulation of meiotic progression by Sertoli-cell androgen signaling.
Document Type
Article
Publication Date
12-1-2020
Keywords
JMG
JAX Source
Mol Biol Cell 2020 Dec 1; 31(25):2841-2862
Volume
31
Issue
25
First Page
2841
Last Page
2862
ISSN
1939-4586
PMID
33026960
DOI
https://doi.org/10.1016/j.cell.2020.10.045
Abstract
Cancer therapies kill tumors either directly or indirectly by evoking immune responses and have been combined with varying levels of success. Here, we describe a paradigm to control cancer growth that is based on both direct tumor killing and the triggering of protective immunity. Genetic ablation of serine protease inhibitor SerpinB9 (Sb9) results in the death of tumor cells in a granzyme B (GrB)-dependent manner. Sb9-deficient mice exhibited protective T cell-based host immunity to tumors in association with a decline in GrB-expressing immunosuppressive cells within the tumor microenvironment (TME). Maximal protection against tumor development was observed when the tumor and host were deficient in Sb9. The therapeutic utility of Sb9 inhibition was demonstrated by the control of tumor growth, resulting in increased survival times in mice. Our studies describe a molecular target that permits a combination of tumor ablation, interference within the TME, and immunotherapy in one potential modality.
Recommended Citation
Larose H,
Kent T,
Ma Q,
Shami A,
Harerimana N,
Li J,
Hammoud S,
Handel M.
Regulation of meiotic progression by Sertoli-cell androgen signaling. Mol Biol Cell 2020 Dec 1; 31(25):2841-2862