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

Publication date: April 2017
Source:European Journal of Cancer, Volume 75
Author(s): Julia K. Tietze, Daniela Angelova, Markus V. Heppt, Markus Reinholz, William J. Murphy, Michael Spannagl, Thomas Ruzicka, Carola Berking
BackgroundImmune 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.MethodsWe 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.ResultsWe 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.ConclusionPatients 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.



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