Association of antigen-specific T-cell responses with antigen expression and immunoparalysis in multiple myeloma
Purpose: Cancer testis antigens (CTA) are immunotherapeutical targets aberrantly expressed on multiple myeloma cells, especially at later stages, when a concomitant immunoparesis hampers vaccination approaches. - Experimental Design: We assessed the expression of the multiple myeloma antigen HM1.24...
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| Hauptverfasser: | , , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
January 21, 2015
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| In: |
Clinical cancer research
Year: 2015, Jahrgang: 21, Heft: 7, Pages: 1712-1721 |
| ISSN: | 1557-3265 |
| DOI: | 10.1158/1078-0432.CCR-14-1618 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1158/1078-0432.CCR-14-1618 Verlag, lizenzpflichtig, Volltext: https://clincancerres.aacrjournals.org/content/21/7/1712 
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| Verfasserangaben: | Sabrina Fichtner, Dirk Hose, Melanie Engelhardt, Tobias Meißner, Brigitte Neuber, Fatime Krasniqi, Marc Raab, Stefan Schönland, Anthony D. Ho, Hartmut Goldschmidt, and Michael Hundemer |
| Zusammenfassung: | Purpose: Cancer testis antigens (CTA) are immunotherapeutical targets aberrantly expressed on multiple myeloma cells, especially at later stages, when a concomitant immunoparesis hampers vaccination approaches. - Experimental Design: We assessed the expression of the multiple myeloma antigen HM1.24 (reported present in all malignant plasma cells) and the CTAs MAGE-A2/A3 and NY-ESO-1 (aberrantly expressed in a subset of patients with myeloma), in CD138-purified myeloma cells by qRT-PCR (n = 149). In a next step, we analyzed the antigen-specific T-cell responses against these antigens by IFNγ EliSpot assay (n = 145) and granzymeB ELISA (n = 62) in relation to stage (tumor load) and expression of the respective antigen. - Results: HM1.24 is expressed in all plasma-cell samples, whereas CTAs are significantly more frequent in later stages. HM1.24-specific T-cell responses, representing the immunologic status, significantly decreased from healthy donors to advanced disease. For the CTAs, the probability of T-cell responses increased in early and advanced stages compared with healthy donors, paralleling increased probability of expression. In advanced stages, T-cell responses decreased because of immunoparesis. - Conclusion: In conclusion, specific T-cell responses in myeloma are triggered by antigen expression but suppressed by tumor load. Future CTA-based immunotherapeutical approaches might target early plasma-cell diseases to establish prophylactically a specific T-cell response against late-stage antigens in immunocompetent patients. Clin Cancer Res; 21(7); 1712-21. ©2015 AACR. |
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| Beschreibung: | Gesehen am 08.01.2021 |
| Beschreibung: | Online Resource |
| ISSN: | 1557-3265 |
| DOI: | 10.1158/1078-0432.CCR-14-1618 |