Gide and Quek et al. characterized melanoma samples from patients treated with anti-PD-1 or combination anti-PD-1/anti-CTLA-4 and found that in responders tumor infiltration by activated CD8+ T cells likely drove responses. Non-responders to anti-PD-1 often coexpressed other targetable immune checkpoints. A gene expression profile for EOMES+CD69+CD45RO+ effector memory CD4+ or CD8+ T cells was more abundant in responders and associated with longer PFS in anti-PD-1 therapy and greater tumor reduction in both mono- and combination therapy. The presence of this subset was a better predictor of response than PD-L1 or CD8 alone.
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.
Author Info: (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
Author Info: (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. (3) 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. (4) Melanoma Institute Australia, The University of Sydney, Sydney, NSW 2065, Australia. (5) Melanoma Institute Australia, The University of Sydney, Sydney, NSW 2065, Australia. (6) Sydney Medical School, The University of Sydney, Sydney, NSW 2006, Australia; Centenary Institute, The University of Sydney, Sydney, NSW 2050, Australia. (7) Melanoma Institute Australia, The University of Sydney, Sydney, NSW 2065, Australia. (8) Melanoma Institute Australia, The University of Sydney, Sydney, NSW 2065, Australia; Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW 2109, Australia. (9) Melanoma Institute Australia, The University of Sydney, Sydney, NSW 2065, Australia. (10) Oncology Biomarker Development, Genentech Inc, South San Francisco, CA 94080, USA. (11) Oncology Biomarker Development, Genentech Inc, South San Francisco, CA 94080, USA. (12) Melanoma Institute Australia, The University of Sydney, Sydney, NSW 2065, Australia. (13) 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. (14) 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. (15) 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. (16) Sydney Medical School, The University of Sydney, Sydney, NSW 2006, Australia; Centenary Institute, The University of Sydney, Sydney, NSW 2050, Australia. (17) 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. (18) Sydney Medical School, The University of Sydney, Sydney, NSW 2006, Australia; Centenary Institute, The University of Sydney, Sydney, NSW 2050, Australia. (19) 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. (20) Melanoma Institute Australia, The University of Sydney, Sydney, NSW 2065, Australia; Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW 2109, Australia. (21) Melanoma Institute Australia, The University of Sydney, Sydney, NSW 2065, Australia; Sydney Medical School, The University of Sydney, Sydney, NSW 2006, Australia. (22) Melanoma Institute Australia, The University of Sydney, Sydney, NSW 2065, Australia; Sydney Medical School, The University of Sydney, Sydney, NSW 2006, Australia. (23) 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. (24) 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. (25) 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.
