Donor lymphocyte infusion leads to diversity of specific T cell responses and reduces regulatory T cell frequency in clinical responders
T cell responses against malignant cells play a major role in maintaining remission and prolonging overall survival in patients after allogeneic stem cell transplantation and donor lymphocyte infusion (DLI) due to graft-versus-leukemia effect. For better characterization of the T cell responses, we...
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| Main Authors: | , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
2019
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| In: |
International journal of cancer
Year: 2019, Volume: 144, Issue: 5, Pages: 1135-1146 |
| ISSN: | 1097-0215 |
| DOI: | 10.1002/ijc.31753 |
| Online Access: | Verlag, Volltext: http://dx.doi.org/10.1002/ijc.31753 Verlag, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/ijc.31753 
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| Author Notes: | Susanne Hofmann, Michael Schmitt, Marlies Götz, Hartmut Döhner, Markus Wiesneth, Donald Bunjes and Jochen Greiner |
| Summary: | T cell responses against malignant cells play a major role in maintaining remission and prolonging overall survival in patients after allogeneic stem cell transplantation and donor lymphocyte infusion (DLI) due to graft-versus-leukemia effect. For better characterization of the T cell responses, we assessed frequency and diversity of leukemia-associated antigen (LAA)-specific cytotoxic T cells using ELISpot and pMHC multimer assays and analyzed the frequency of regulatory T cells (Treg) as well as cytokine profiles before/after DLI. The data were correlated to the clinical course of patients. Significantly more LAA-derived T cell epitopes (p = 0.02) were recognized in clinical responders (R) when compared to nonresponders (NR). In addition, pMHC multimer-based flow cytometry showed a significantly higher frequency of LAA-specific T cells in R versus NR. The frequency of Treg in R decreased significantly (p = 0.008) while keeping stable in NR. No differences in T cell subset analysis before/after DLI were revealed. Clinical responders were correlated to specific immune responses and all clinical responders showed an increase of specific immune responses after DLI. Cytokine assays using enzyme-linked immunosorbent assay showed a significant increase of IL-4 after DLI. Taken together, an increase of specific CTL responses against several LAA after DLI was detected. Moreover, this study suggests that enhanced LAA diversity in T cell responses as well as decreasing numbers of Treg contribute to clinical outcome of patients treated with DLI. |
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| Item Description: | Online 14 Jul 2018 Gesehen am 15.02.2019 |
| Physical Description: | Online Resource |
| ISSN: | 1097-0215 |
| DOI: | 10.1002/ijc.31753 |