Direct Tumor Killing and Immunotherapy through Anti-SerpinB9 Therapy.
Document Type
Article
Publication Date
11-25-2020
Keywords
JMG, JAXCC
JAX Source
Cell 2020 Nov 25; 183(5):1219-1233.e18
Volume
183
Issue
5
First Page
1219
Last Page
1233
ISSN
1097-4172
PMID
33242418
DOI
https://doi.org/10.1016/j.cell.2020.10.045
Grant
AI132963; OD018259; CA034196
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
Jiang L,
Wang Y,
Zhao J,
Uehara M,
Hou Q,
Kasinath V,
Ichimura T,
Banouni N,
Dai L,
Li X,
Greiner D,
Shultz LD,
Zhang X,
Sun Z,
Curtin I,
Vangos N,
Yeoh Z,
Geffken E,
Seo H,
Liu Z,
Heffron G,
Shah K,
Dhe-Paganon S,
Abdi R.
Direct Tumor Killing and Immunotherapy through Anti-SerpinB9 Therapy. Cell 2020 Nov 25; 183(5):1219-1233.e18