Details

Autor(en) / Beteiligte

• Gide, Tuba N.
• Quek, Camelia
• Menzies, Alexander M.
• Tasker, Annie T.
• Shang, Ping
• Holst, Jeff
• Madore, Jason
• Lim, Su Yin
• Velickovic, Rebecca
• Wongchenko, Matthew
• Yan, Yibing
• Lo, Serigne
• Carlino, Matteo S.
• Guminski, Alexander
• Saw, Robyn P.M.
• Pang, Angel
• McGuire, Helen M.
• Palendira, Umaimainthan
• Thompson, John F.
• Rizos, Helen
• Silva, Ines Pires da
• Batten, Marcel
• Scolyer, Richard A.
• Long, Georgina V.
• Wilmott, James S.

Titel

Distinct Immune Cell Populations Define Response to Anti-PD-1 Monotherapy and Anti-PD-1/Anti-CTLA-4 Combined Therapy

Ist Teil von

• Cancer cell, 2019-02, Vol.35 (2), p.238-255.e6

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2019

Quelle

MEDLINE

Beschreibungen/Notizen

• Cancer immunotherapies provide survival benefits in responding patients, but many patients fail to respond. Identifying the biology of treatment response and resistance are a priority to optimize drug selection and improve patient outcomes. We performed transcriptomic and immune profiling on 158 tumor biopsies from melanoma patients treated with anti-PD-1 monotherapy (n = 63) or combined anti-PD-1 and anti-CTLA-4 (n = 57). These data identified activated T cell signatures and T cell populations in responders to both treatments. Further mass cytometry analysis identified an EOMES+CD69+CD45RO+ effector memory T cell phenotype that was significantly more abundant in responders to combined immunotherapy compared with non-responders (n = 18). The gene expression profile of this population was associated with longer progression-free survival in patients treated with single agent and greater tumor shrinkage in both treatments. [Display omitted] •Activated T cell signatures/populations drive response to anti-PD-1-based therapies•EOMES+CD69+CD45RO+ effector memory T cells are associated with response•EOMES+CD69+CD45RO+ expression is associated with longer PFS and tumor shrinkage•Non-responders with TIL-hot tumors express other immune drug targets Gide et al. characterize melanoma samples from patients treated with anti-PD-1 alone or with anti-CTLA-4. Tumors from non-responders to monotherapy often express other immune checkpoints and higher gene expression profile of EOMES+CD69+CD45RO+ T cells is associated with greater tumor shrinkage in both therapies.