The proportion of circulating CD45RO+CD8+ memory T cells is correlated with clinical response in melanoma patients treated with ipilimumab

Julia K. Tietze, Daniela Angelova, Markus V. Heppt, Markus Reinholz, William J Murphy, Michael Spannagl, Thomas Ruzicka, Carola Berking

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Background Immune checkpoint blockade (ICB) has been a breakthrough in the treatment of metastatic melanoma. But with only about 20–40% long-term responders and severe side-effects in about 12–17%, finding predictive markers for treatment response is of great interest. Methods We prospectively assessed clinical data, haematologic parameters and freshly isolated peripheral blood mononuclear cells of 30 patients treated with ipilimumab (n = 21) and pembrolizumab (n = 9) prior to the first 4 cycles with ICB and before the first tumour assessment. Results We discovered that the baseline levels of CD45RO+CD8+ T cells significantly differed among the patients. Thirteen (43%) of our patients had normal baseline levels of CD45RO+CD8+ T cells, whereas 17 (57%) patients were low on CD45RO+CD8+ T cells. The baseline levels of CD45RO+CD8+ T cells correlated significantly with the response to ipilimumab but not pembrolizumab. Patients with baseline levels of lower/equal 25% of CD45RO+CD8+ T cells did not respond to treatment with ipilimumab. Phenotyping the CD8+ T cells in patients treated with ipilimumab revealed an activated HLA-DR+CD25 phenotype, implying antigen non-specific stimulation. The levels of the HLA-DR+CD25CD8+ T cells were significantly higher in patients with a normal baseline of CD45RO+CD8+ T cells and even increased significantly during treatment. Furthermore, proliferation of melanoma antigen recognized by T cells 1 (MART-1)-specific CD8+ T cells was not observed. Patients with normal baseline levels of CD45RO+CD8+ T cells showed a significant longer overall survival when treated with ipilimumab but not pembrolizumab. Conclusion Patients with normal baseline levels of CD45RO+CD8+ T cells respond significantly more frequently to treatment with ipilimumab and the CD8+ T cells appear to be antigen non-specifically activated. The baseline level of CD45RO+CD8+ T cells represents a promising factor as biomarker for the prediction of the response to ipilimumab.

Original languageEnglish (US)
Pages (from-to)268-279
Number of pages12
JournalEuropean Journal of Cancer
Volume75
DOIs
StatePublished - Apr 1 2017

Fingerprint

Melanoma
T-Lymphocytes
HLA-DR Antigens
ipilimumab
MART-1 Antigen
Therapeutics
Antigens
Biomarkers
Phenotype
Survival

Keywords

  • CD45ROCD8 T cells
  • HLA-DRCD25CD8 phenotype
  • Immune checkpoint blockade
  • Ipilimumab
  • Melanoma
  • Pembrolizumab
  • Predictive marker

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

The proportion of circulating CD45RO+CD8+ memory T cells is correlated with clinical response in melanoma patients treated with ipilimumab. / Tietze, Julia K.; Angelova, Daniela; Heppt, Markus V.; Reinholz, Markus; Murphy, William J; Spannagl, Michael; Ruzicka, Thomas; Berking, Carola.

In: European Journal of Cancer, Vol. 75, 01.04.2017, p. 268-279.

Research output: Contribution to journalArticle

Tietze, Julia K. ; Angelova, Daniela ; Heppt, Markus V. ; Reinholz, Markus ; Murphy, William J ; Spannagl, Michael ; Ruzicka, Thomas ; Berking, Carola. / The proportion of circulating CD45RO+CD8+ memory T cells is correlated with clinical response in melanoma patients treated with ipilimumab. In: European Journal of Cancer. 2017 ; Vol. 75. pp. 268-279.
@article{0c71f67a3ef74a7399ec37ab9f7335a8,
title = "The proportion of circulating CD45RO+CD8+ memory T cells is correlated with clinical response in melanoma patients treated with ipilimumab",
abstract = "Background Immune checkpoint blockade (ICB) has been a breakthrough in the treatment of metastatic melanoma. But with only about 20–40{\%} long-term responders and severe side-effects in about 12–17{\%}, finding predictive markers for treatment response is of great interest. Methods We prospectively assessed clinical data, haematologic parameters and freshly isolated peripheral blood mononuclear cells of 30 patients treated with ipilimumab (n = 21) and pembrolizumab (n = 9) prior to the first 4 cycles with ICB and before the first tumour assessment. Results We discovered that the baseline levels of CD45RO+CD8+ T cells significantly differed among the patients. Thirteen (43{\%}) of our patients had normal baseline levels of CD45RO+CD8+ T cells, whereas 17 (57{\%}) patients were low on CD45RO+CD8+ T cells. The baseline levels of CD45RO+CD8+ T cells correlated significantly with the response to ipilimumab but not pembrolizumab. Patients with baseline levels of lower/equal 25{\%} of CD45RO+CD8+ T cells did not respond to treatment with ipilimumab. Phenotyping the CD8+ T cells in patients treated with ipilimumab revealed an activated HLA-DR+CD25− phenotype, implying antigen non-specific stimulation. The levels of the HLA-DR+CD25−CD8+ T cells were significantly higher in patients with a normal baseline of CD45RO+CD8+ T cells and even increased significantly during treatment. Furthermore, proliferation of melanoma antigen recognized by T cells 1 (MART-1)-specific CD8+ T cells was not observed. Patients with normal baseline levels of CD45RO+CD8+ T cells showed a significant longer overall survival when treated with ipilimumab but not pembrolizumab. Conclusion Patients with normal baseline levels of CD45RO+CD8+ T cells respond significantly more frequently to treatment with ipilimumab and the CD8+ T cells appear to be antigen non-specifically activated. The baseline level of CD45RO+CD8+ T cells represents a promising factor as biomarker for the prediction of the response to ipilimumab.",
keywords = "CD45ROCD8 T cells, HLA-DRCD25CD8 phenotype, Immune checkpoint blockade, Ipilimumab, Melanoma, Pembrolizumab, Predictive marker",
author = "Tietze, {Julia K.} and Daniela Angelova and Heppt, {Markus V.} and Markus Reinholz and Murphy, {William J} and Michael Spannagl and Thomas Ruzicka and Carola Berking",
year = "2017",
month = "4",
day = "1",
doi = "10.1016/j.ejca.2016.12.031",
language = "English (US)",
volume = "75",
pages = "268--279",
journal = "European Journal of Cancer",
issn = "0959-8049",
publisher = "Elsevier Limited",

}

TY - JOUR

T1 - The proportion of circulating CD45RO+CD8+ memory T cells is correlated with clinical response in melanoma patients treated with ipilimumab

AU - Tietze, Julia K.

AU - Angelova, Daniela

AU - Heppt, Markus V.

AU - Reinholz, Markus

AU - Murphy, William J

AU - Spannagl, Michael

AU - Ruzicka, Thomas

AU - Berking, Carola

PY - 2017/4/1

Y1 - 2017/4/1

N2 - Background Immune checkpoint blockade (ICB) has been a breakthrough in the treatment of metastatic melanoma. But with only about 20–40% long-term responders and severe side-effects in about 12–17%, finding predictive markers for treatment response is of great interest. Methods We prospectively assessed clinical data, haematologic parameters and freshly isolated peripheral blood mononuclear cells of 30 patients treated with ipilimumab (n = 21) and pembrolizumab (n = 9) prior to the first 4 cycles with ICB and before the first tumour assessment. Results We discovered that the baseline levels of CD45RO+CD8+ T cells significantly differed among the patients. Thirteen (43%) of our patients had normal baseline levels of CD45RO+CD8+ T cells, whereas 17 (57%) patients were low on CD45RO+CD8+ T cells. The baseline levels of CD45RO+CD8+ T cells correlated significantly with the response to ipilimumab but not pembrolizumab. Patients with baseline levels of lower/equal 25% of CD45RO+CD8+ T cells did not respond to treatment with ipilimumab. Phenotyping the CD8+ T cells in patients treated with ipilimumab revealed an activated HLA-DR+CD25− phenotype, implying antigen non-specific stimulation. The levels of the HLA-DR+CD25−CD8+ T cells were significantly higher in patients with a normal baseline of CD45RO+CD8+ T cells and even increased significantly during treatment. Furthermore, proliferation of melanoma antigen recognized by T cells 1 (MART-1)-specific CD8+ T cells was not observed. Patients with normal baseline levels of CD45RO+CD8+ T cells showed a significant longer overall survival when treated with ipilimumab but not pembrolizumab. Conclusion Patients with normal baseline levels of CD45RO+CD8+ T cells respond significantly more frequently to treatment with ipilimumab and the CD8+ T cells appear to be antigen non-specifically activated. The baseline level of CD45RO+CD8+ T cells represents a promising factor as biomarker for the prediction of the response to ipilimumab.

AB - Background Immune checkpoint blockade (ICB) has been a breakthrough in the treatment of metastatic melanoma. But with only about 20–40% long-term responders and severe side-effects in about 12–17%, finding predictive markers for treatment response is of great interest. Methods We prospectively assessed clinical data, haematologic parameters and freshly isolated peripheral blood mononuclear cells of 30 patients treated with ipilimumab (n = 21) and pembrolizumab (n = 9) prior to the first 4 cycles with ICB and before the first tumour assessment. Results We discovered that the baseline levels of CD45RO+CD8+ T cells significantly differed among the patients. Thirteen (43%) of our patients had normal baseline levels of CD45RO+CD8+ T cells, whereas 17 (57%) patients were low on CD45RO+CD8+ T cells. The baseline levels of CD45RO+CD8+ T cells correlated significantly with the response to ipilimumab but not pembrolizumab. Patients with baseline levels of lower/equal 25% of CD45RO+CD8+ T cells did not respond to treatment with ipilimumab. Phenotyping the CD8+ T cells in patients treated with ipilimumab revealed an activated HLA-DR+CD25− phenotype, implying antigen non-specific stimulation. The levels of the HLA-DR+CD25−CD8+ T cells were significantly higher in patients with a normal baseline of CD45RO+CD8+ T cells and even increased significantly during treatment. Furthermore, proliferation of melanoma antigen recognized by T cells 1 (MART-1)-specific CD8+ T cells was not observed. Patients with normal baseline levels of CD45RO+CD8+ T cells showed a significant longer overall survival when treated with ipilimumab but not pembrolizumab. Conclusion Patients with normal baseline levels of CD45RO+CD8+ T cells respond significantly more frequently to treatment with ipilimumab and the CD8+ T cells appear to be antigen non-specifically activated. The baseline level of CD45RO+CD8+ T cells represents a promising factor as biomarker for the prediction of the response to ipilimumab.

KW - CD45ROCD8 T cells

KW - HLA-DRCD25CD8 phenotype

KW - Immune checkpoint blockade

KW - Ipilimumab

KW - Melanoma

KW - Pembrolizumab

KW - Predictive marker

UR - http://www.scopus.com/inward/record.url?scp=85013766835&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85013766835&partnerID=8YFLogxK

U2 - 10.1016/j.ejca.2016.12.031

DO - 10.1016/j.ejca.2016.12.031

M3 - Article

C2 - 28242504

AN - SCOPUS:85013766835

VL - 75

SP - 268

EP - 279

JO - European Journal of Cancer

JF - European Journal of Cancer

SN - 0959-8049

ER -