Cover Image

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...

Full description

Saved in:
Bibliographic Details
Main Authors: Fichtner, Sabrina (Author) , Hose, Dirk (Author) , Engelhardt, Melanie (Author) , Meißner, Tobias (Author) , Neuber, Brigitte (Author) , Krasniqi, Fatime (Author) , Raab, Marc-Steffen (Author) , Schönland, Stefan (Author) , Ho, Anthony Dick (Author) , Goldschmidt, Hartmut (Author) , Hundemer, Michael (Author)
Format: Article (Journal)
Language:English
Published: January 21, 2015
In: Clinical cancer research
Year: 2015, Volume: 21, Issue: 7, Pages: 1712-1721
ISSN:1557-3265
DOI:10.1158/1078-0432.CCR-14-1618
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1158/1078-0432.CCR-14-1618
Verlag, lizenzpflichtig, Volltext: https://clincancerres.aacrjournals.org/content/21/7/1712
Get full text
Author Notes:Sabrina Fichtner, Dirk Hose, Melanie Engelhardt, Tobias Meißner, Brigitte Neuber, Fatime Krasniqi, Marc Raab, Stefan Schönland, Anthony D. Ho, Hartmut Goldschmidt, and Michael Hundemer
Description
Summary: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.
Item Description:Gesehen am 08.01.2021
Physical Description:Online Resource
ISSN:1557-3265
DOI:10.1158/1078-0432.CCR-14-1618

Similar Items