Cancer-Germline Antigen Expression Discriminates Clinical Outcome to CTLA-4 Blockade | Zendy

Sachet A. Shukla | Zendy; Pavan Bachireddy | Zendy; Bastian Schilling | Zendy; Christina Galonska | Zendy; Qian Zhan | Zendy; Clyde Bango | Zendy; Rupert Langer | Zendy; Patrick Lee | Zendy; Daniel Gusenleitner | Zendy; Derin B. Keskin | Zendy; Mehrtash Babadi | Zendy; Arman W. Mohammad | Zendy; Andreas Gnirke | Zendy; Kendell Clement | Zendy; Zachary Cartun | Zendy; Eliezer M. Van Allen | Zendy; Diana Miao | Zendy; Ying Huang | Zendy; Alexandra Snyder | Zendy; Taha Merghoub | Zendy; Jedd D. Wolchok | Zendy; Levi A. Garraway | Zendy; Alexander Meissner | Zendy; Jeffrey S. Weber | Zendy; Nir Hacohen | Zendy; Doneuberg | Zendy; Patrick Ryan Potts | Zendy; Gëorge F. Murphy | Zendy; Christine G. Lian | Zendy; Dirk Schadendorf | Zendy; F. Stephen Hodi | Zendy; Catherine J. Wu | Zendy

AI Assistant Blog Pricing

Home ZAIA Blog

Open Access

Cancer-Germline Antigen Expression Discriminates Clinical Outcome to CTLA-4 Blockade

Author(s) -

Sachet A. Shukla,

Pavan Bachireddy,

Bastian Schilling,

Christina Galonska,

Qian Zhan,

Clyde Bango,

Rupert Langer,

Patrick Lee,

Daniel Gusenleitner,

Derin B. Keskin,

Mehrtash Babadi,

Arman W. Mohammad,

Andreas Gnirke,

Kendell Clement,

Zachary Cartun,

Eliezer M. Van Allen,

Diana Miao,

Ying Huang,

Alexandra Snyder,

Taha Merghoub,

Jedd D. Wolchok,

Levi A. Garraway,

Alexander Meissner,

Jeffrey S. Weber,

Nir Hacohen,

Doneuberg,

Patrick Ryan Potts,

Gëorge F. Murphy,

Christine G. Lian,

Dirk Schadendorf,

F. Stephen Hodi,

Catherine J. Wu

Publication year - 2018

Publication title -

cell

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 26.304

H-Index - 776

eISSN - 1097-4172

pISSN - 0092-8674

DOI - 10.1016/j.cell.2018.03.026

Subject(s) - biology , ctla 4 , germline , blockade , antigen , cancer , expression (computer science) , cancer research , genetics , immunology , immune system , gene , t cell , receptor , computer science , programming language

CTLA-4 immune checkpoint blockade is clinically effective in a subset of patients with metastatic melanoma. We identify a subcluster of MAGE-A cancer-germline antigens, located within a narrow 75 kb region of chromosome Xq28, that predicts resistance uniquely to blockade of CTLA-4, but not PD-1. We validate this gene expression signature in an independent anti-CTLA-4-treated cohort and show its specificity to the CTLA-4 pathway with two independent anti-PD-1-treated cohorts. Autophagy, a process critical for optimal anti-cancer immunity, has previously been shown to be suppressed by the MAGE-TRIM28 ubiquitin ligase in vitro. We now show that the expression of the key autophagosome component LC3B and other activators of autophagy are negatively associated with MAGE-A protein levels in human melanomas, including samples from patients with resistance to CTLA-4 blockade. Our findings implicate autophagy suppression in resistance to CTLA-4 blockade in melanoma, suggesting exploitation of autophagy induction for potential therapeutic synergy with CTLA-4 inhibitors.

The content you want is available to Zendy users.

Already have an account? Click here to sign in.

Having issues? You can contact us here

Accelerating Research