Engineering T cell response to cancer antigens by choice of focal therapeutic conditions

Autor: Qi Shao, Stephen O'Flanagan, Tiffany Lam, Priyatanu Roy, Francisco Pelaez, Brandon J Burbach, Samira M Azarin, Yoji Shimizu, John C Bischof
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: International Journal of Hyperthermia, Vol 36, Iss 1, Pp 130-138 (2019)
Druh dokumentu: article
ISSN: 0265-6736
1464-5157
02656736
DOI: 10.1080/02656736.2018.1539253
Popis: Focal thermal therapy (Heat), cryosurgery (Cryo) and irreversible electroporation (IRE) are increasingly used to treat cancer. However, local recurrence and systemic spread are persistent negative outcomes. Nevertheless, emerging work with immunotherapies (i.e., checkpoint blockade or dendritic cell (DC) vaccination) in concert with focal therapies may improve outcomes. To understand the role of focal therapy in priming the immune system for immunotherapy, an in vitro model of T cell response after exposure to B16 melanoma cell lysates after lethal exposures was designed. Exposure included: Heat (50 °C, 30 min), Cryo (−80 °C, 30 min) and IRE (1250 V/cm, 99 pulses, 50 µs pulses with 1 Hz intervals). After viability assessment (CCK-8 assay), cell lysates were collected and assessed for protein release (BCA assay), protein denaturation (FTIR-spectroscopy), TRP-2 antigen release (western blot), and T cell activation (antigen-specific CD8 T cell proliferation). Results showed IRE released the most protein and antigen (TRP-2), followed by Cryo and Heat. In contrast, Cryo released the most native (not denatured) protein, compared to IRE and Heat. Finally, IRE dramatically outperformed both Cryo and Heat in T cell activation while Cryo modestly outperformed Heat. This study demonstrates that despite all focal therapies ability to destroy cells, the ‘quantity’ (i.e., amount) and ‘quality’ (i.e., molecular state) of tumor protein (including antigen) released can dramatically change the ensuing priming of the immune system. This suggests protein-based metrics whereby focal therapies can be designed to prime the immune system in concert with immunotherapies to eventually achieve improved and durable cancer treatment in vivo.
Databáze: Directory of Open Access Journals
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