Cancer testis antigens are immunotherapeutical targets aberrantly expressed on multiple myeloma cells, especially at later stages, when a concomitant immunoparesis hampers vaccination approaches. We assessed the expression of the multiple myeloma antigen HM1.24 (reported present in all malignant plasma-cells) and the cancer testis antigens MAGE-A2/A3 and NY-ESO-1 (aberrantly expressed in a subset of myeloma patients), 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 IFN-γ EliSpot-assay (n=145) and granzymeB ELISA (n=62) in relation to stage (tumor load) and expression of the respective antigen. HM1.24 is expressed in all plasma-cell samples, whereas cancer testis antigens are significantly more frequent in later stages. HM1.24 specific T-cell responses, representing the immunological status, significantly decreased from healthy donors to advanced disease. For the cancer testis antigens, the probability of T-cell responses increased in early and advanced stages compared to healthy donors, paralleling increased probability of expression. In advanced stages, T-cell responses decreased due to immunoparesis. In conclusion, specific T-cell responses in myeloma are triggered by antigen-expression but suppressed by tumor load. Future cancer testis antigen-based immunotherpeutical approaches might target early plasmacell-diseases to establish prophylactically a specific T-cell response against late stage antigens in immunocompetent patients.
- Received June 24, 2014.
- Revision received December 23, 2014.
- Accepted December 31, 2014.
- Copyright © 2015, American Association for Cancer Research.