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

Tuba N Gide¹, Camelia Quek¹, Alexander M Menzies², Annie T Tasker³, Ping Shang³, Jeff Holst⁴, Jason Madore³, Su Yin Lim⁵, Rebecca Velickovic³, Matthew Wongchenko⁶, Yibing Yan⁶, Serigne Lo³, Matteo S Carlino⁷, Alexander Guminski², Robyn P M Saw⁸, Angel Pang⁴, Helen M McGuire⁹, Umaimainthan Palendira⁴, John F Thompson⁸, Helen Rizos⁵, Ines Pires da Silva¹, Marcel Batten¹, Richard A Scolyer⁸, Georgina V Long², James S Wilmott¹⁰

Affiliations

¹ Melanoma Institute Australia, The University of Sydney, Sydney, NSW 2065, Australia; Sydney Medical School, The University of Sydney, Sydney, NSW 2006, Australia.
² Melanoma Institute Australia, The University of Sydney, Sydney, NSW 2065, Australia; Sydney Medical School, The University of Sydney, Sydney, NSW 2006, Australia; Department of Medical Oncology, Royal North Shore Hospital, Sydney, NSW 2065, Australia; Department of Medical Oncology, Mater Hospital, North Sydney, NSW 2060, Australia.
³ Melanoma Institute Australia, The University of Sydney, Sydney, NSW 2065, Australia.
⁴ Sydney Medical School, The University of Sydney, Sydney, NSW 2006, Australia; Centenary Institute, The University of Sydney, Sydney, NSW 2050, Australia.
⁵ Melanoma Institute Australia, The University of Sydney, Sydney, NSW 2065, Australia; Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW 2109, Australia.
⁶ Oncology Biomarker Development, Genentech Inc, South San Francisco, CA 94080, USA.
⁷ Melanoma Institute Australia, The University of Sydney, Sydney, NSW 2065, Australia; Sydney Medical School, The University of Sydney, Sydney, NSW 2006, Australia; Crown Princess Mary Cancer Centre, Westmead and Blacktown Hospitals, Sydney, NSW 2145, Australia.
⁸ Melanoma Institute Australia, The University of Sydney, Sydney, NSW 2065, Australia; Sydney Medical School, The University of Sydney, Sydney, NSW 2006, Australia; Royal Prince Alfred Hospital, Sydney, NSW 2050, Australia.
⁹ Ramaciotti Facility for Human Systems Biology, Charles Perkins Centre, The University of Sydney, Sydney, NSW 2006, Australia; Discipline of Pathology, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2006, Australia.
¹⁰ Melanoma Institute Australia, The University of Sydney, Sydney, NSW 2065, Australia; Sydney Medical School, The University of Sydney, Sydney, NSW 2006, Australia. Electronic address: james.wilmott@melanoma.org.au.

PMID: 30753825
DOI: 10.1016/j.ccell.2019.01.003

Free article

Comparative Study

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

Tuba N Gide et al. Cancer Cell. 2019.

Free article

. 2019 Feb 11;35(2):238-255.e6.

doi: 10.1016/j.ccell.2019.01.003.

Authors

Affiliations

¹ Melanoma Institute Australia, The University of Sydney, Sydney, NSW 2065, Australia; Sydney Medical School, The University of Sydney, Sydney, NSW 2006, Australia.
² Melanoma Institute Australia, The University of Sydney, Sydney, NSW 2065, Australia; Sydney Medical School, The University of Sydney, Sydney, NSW 2006, Australia; Department of Medical Oncology, Royal North Shore Hospital, Sydney, NSW 2065, Australia; Department of Medical Oncology, Mater Hospital, North Sydney, NSW 2060, Australia.
³ Melanoma Institute Australia, The University of Sydney, Sydney, NSW 2065, Australia.
⁴ Sydney Medical School, The University of Sydney, Sydney, NSW 2006, Australia; Centenary Institute, The University of Sydney, Sydney, NSW 2050, Australia.
⁵ Melanoma Institute Australia, The University of Sydney, Sydney, NSW 2065, Australia; Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW 2109, Australia.
⁶ Oncology Biomarker Development, Genentech Inc, South San Francisco, CA 94080, USA.
⁷ Melanoma Institute Australia, The University of Sydney, Sydney, NSW 2065, Australia; Sydney Medical School, The University of Sydney, Sydney, NSW 2006, Australia; Crown Princess Mary Cancer Centre, Westmead and Blacktown Hospitals, Sydney, NSW 2145, Australia.
⁸ Melanoma Institute Australia, The University of Sydney, Sydney, NSW 2065, Australia; Sydney Medical School, The University of Sydney, Sydney, NSW 2006, Australia; Royal Prince Alfred Hospital, Sydney, NSW 2050, Australia.
⁹ Ramaciotti Facility for Human Systems Biology, Charles Perkins Centre, The University of Sydney, Sydney, NSW 2006, Australia; Discipline of Pathology, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2006, Australia.
¹⁰ Melanoma Institute Australia, The University of Sydney, Sydney, NSW 2065, Australia; Sydney Medical School, The University of Sydney, Sydney, NSW 2006, Australia. Electronic address: james.wilmott@melanoma.org.au.

PMID: 30753825
DOI: 10.1016/j.ccell.2019.01.003

Abstract

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.

Keywords: EOMES; RNA-seq; anti-CTLA-4; anti-PD-1; combination therapy; immune checkpoint inhibitors; immunotherapy; melanoma; predictive biomarkers; resistance mechanisms.

PubMed Disclaimer

Publication types

Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

LinkOut - more resources

Full Text Sources
- Elsevier Science
Other Literature Sources
- The Lens - Patent Citations Database
Medical
- MedlinePlus Health Information

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

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

Affiliations

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

Authors

Affiliations

Abstract

Publication types

MeSH terms

Substances

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical