Peripheral CD8 effector-memory type 1 T-cells correlate with outcome in ipilimumab-treated stage IV melanoma patients.
The role of the assessment of peripheral T-cell phenotypes in predicting overall survival (OS) after ipilimumab treatment is unclear. Here, we analysed mononuclear cells in the blood before and at different time points during treatment with ipilimumab in 137 late-stage melanoma patients. The proportions of baseline naïve and memory T-cells were measured by flow cytometry and correlated with OS, with an emphasis on PD-1 expression. High frequencies (>13%) of CD8 effector-memory type 1 (EM1) T-cells at baseline correlated with longer OS (p = 0.029) and higher clinical response rates (p = 0.01). The frequency of these EM1 cells and the M category had independent impacts on OS (hazard ratio = 1.5, p = 0.033; and hazard ratio = 1.9, p = 0.007). In contrast, high baseline frequencies of late stage-differentiated effector memory CD8 cells (>23.8%) were negatively associated with OS (p = 0.034) but did not correlate with clinical response. Following treatment, a decrease of CD8 cells from baseline to the time of the second drug dose and at later time points was strongly and consistently correlated with a high clinical response rate. Our observations thus suggest an important predictive role of baseline CD8 EM1 cells and changes in CD8 cells for clinical response of ipilimumab. Further validation of these biomarker candidates is warranted.
Department of Dermatology, University Medical Center, Tübingen, Germany; Department of Internal Medicine II, University Medical Center, Tübingen, Germany. Electronic address: kilian.wistuba-hamprecht@uni-tuebingen.de.
Kilian
K
Wistuba-Hamprecht
Department of Dermatology, University Medical Center, Tübingen, Germany; Department of Internal Medicine II, University Medical Center, Tübingen, Germany.
Alexander
A
Martens
Department of Internal Medicine II, University Medical Center, Tübingen, Germany.
Florian
F
Heubach
Department of Oncology, Immunotherapy Unit, INSERM U932, Institut Curie, Paris, France.
Emanuela
E
Romano
The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Marnix
M
Geukes Foppen
Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Jianda
J
Yuan
Memorial Sloan Kettering Cancer Center, New York, NY, USA; Weill Cornell Medical College, New York, NY, USA.
Michael
M
Postow
Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Phillip
P
Wong
Istituto Nazionale Tumori Fondazione Pascale, Naples, Italy.
Domenico
D
Mallardo
Department of Dermatology, University Hospital, West German Cancer Center, University Duisburg-Essen, Essen, Germany; German Cancer Consortium (DKTK), Heidelberg, Germany.
Bastian
B
Schilling
Division of Medical Oncology and Immunotherapy, University Hospital of Siena, Italy.
Anna Maria
AM
Di Giacomo
Department of Oncodermatology, INSERM Research Unit 892, University Hospital, Nantes, France.
Amir
A
Khammari
Department of Oncodermatology, INSERM Research Unit 892, University Hospital, Nantes, France.
Brigitte
B
Dreno
Division of Medical Oncology and Immunotherapy, University Hospital of Siena, Italy.
Michele
M
Maio
Department of Dermatology, University Hospital, West German Cancer Center, University Duisburg-Essen, Essen, Germany; German Cancer Consortium (DKTK), Heidelberg, Germany.
Dirk
D
Schadendorf
Istituto Nazionale Tumori Fondazione Pascale, Naples, Italy.
Paolo A
PA
Ascierto
Memorial Sloan Kettering Cancer Center, New York, NY, USA; Weill Cornell Medical College, New York, NY, USA.
Jedd D
JD
Wolchok
The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Christian U
CU
Blank
Department of Dermatology, University Medical Center, Tübingen, Germany.
Claus
C
Garbe
Department of Internal Medicine II, University Medical Center, Tübingen, Germany; School of Science and Technology, College of Arts and Science, Nottingham Trent University, Nottingham, UK; Division of Cancer Studies, Faculty of Life Sciences and Medicine, King's College London, London, UK.
Graham
G
Pawelec
Department of Dermatology, University Medical Center, Tübingen, Germany.
Benjamin
B
Weide
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000951:Antigens, Neoplasm / Q000378:metabolism; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007156:Immunologic Memory; D000074324:Ipilimumab; D053208:Kaplan-Meier Estimate; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D000074324:Ipilimumab; D061026:Programmed Cell Death 1 Receptor
Biomarker; Effector memory cells; Ipilimumab; Melanoma; Prognosis