Open AccessRIPK1‐mediated immunogenic cell death promotes anti‐tumour immunity against soft‐tissue sarcoma
Author(s) -
Smith Henry G,
Jamal Kunzah,
Dayal Jasbani HS,
Tenev Tencho,
KyulaCurrie Joan,
Guppy Naomi,
Gazinska Patrycja,
Roulstone Victoria,
Liccardi Gianmaria,
Davies Emma,
Roxanis Ioannis,
Melcher Alan A,
Hayes Andrew J,
Inman Gareth J,
Harrington Kevin J,
Meier Pascal
Publication year - 2020
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.201910979
Subject(s) - cancer , breast cancer , library science , medicine , computer science
Drugs that mobilise the immune system against cancer are dramatically improving care for many people. Dying cancer cells play an active role in inducing anti‐tumour immunity but not every form of death can elicit an immune response. Moreover, resistance to apoptosis is a major problem in cancer treatment and disease control. While the term “immunogenic cell death” is not fully defined, activation of receptor‐interacting serine/threonine‐protein kinase 1 (RIPK1) can induce a type of death that mobilises the immune system against cancer. However, no clinical treatment protocols have yet been established that would harness the immunogenic potential of RIPK1. Here, we report the first pre‐clinical application of an in vivo treatment protocol for soft‐tissue sarcoma that directly engages RIPK1‐mediated immunogenic cell death. We find that RIPK1‐mediated cell death significantly improves local disease control, increases activation of CD8 + T cells as well as NK cells, and enhances the survival benefit of immune checkpoint blockade. Our findings warrant a clinical trial to assess the survival benefit of RIPK1‐induced cell death in patients with advanced disease at limb extremities.