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Peripheral CD8 effector-memory type 1 T-cells correlate with outcome in ipilimumab-treated stage IV melanoma patients

Kilian Wistuba-Hamprecht 1, 2, * Alexander Martens 1, 2 Florian Heubach 2 Emanuela Romano 3 Marnix Geukes Foppen 4 Jianda Yuan 5 Michael Postow 5, 6 Phillip Wong 5 Domenico Mallardo 7 Bastian Schilling 8, 9 Anna Di Giacomo 10 Amir Khammari 11 Brigitte Dreno 11 Michele Maio 10 Dirk Schadendorf 8, 9 Paolo Ascierto 7 Jedd Wolchok 5, 6 Christian Blank 4 Claus Garbe 1 Graham Pawelec 2, 12, 13 Benjamin Weide 1
* Corresponding author
1 Department of Dermatology [Tubingen, Germany]
2 Department of Internal Medicine II [Tübingen, Germany]
3 U932 - Immunité et cancer
4 The Netherlands Cancer Institute [Amsterdam, The Netherlands]
5 Memorial Sloane Kettering Cancer Center [New York]
6 Weill Medical College of Cornell University [New York]
7 Istituto Nazionale Tumori Fondazione Pascale [Naples, Italy]
8 Department of Dermatology [Essen, Germany]
9 DKTK - German Cancer Consortium [Heidelberg]
10 Division of Medical Oncology and Immunotherapy [Siena, Italy]
11 CRCNA - Centre de Recherche en Cancérologie Nantes-Angers
12 School of Science and Technology [Nottingham, U.K.]
13 Division of Cancer Studies [London, UK]
Abstract : 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.
Keywords : Effector memory cells Melanoma Prognosis Ipilimumab Biomarker
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https://www.hal.inserm.fr/inserm-01808248
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Submitted on : Tuesday, June 5, 2018 - 3:12:20 PM
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Kilian Wistuba-Hamprecht, Alexander Martens, Florian Heubach, Emanuela Romano, Marnix Geukes Foppen, et al.. Peripheral CD8 effector-memory type 1 T-cells correlate with outcome in ipilimumab-treated stage IV melanoma patients. European Journal of Cancer, Elsevier, 2017, 73, pp.61 - 70. ⟨10.1016/j.ejca.2016.12.011⟩. ⟨inserm-01808248⟩

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