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Blood, 15 October 2008, Vol. 112, No. 8, pp. 3362-3372.
Prepublished online as a Blood First Edition Paper on July 24, 2008; DOI 10.1182/blood-2008-04-149393.
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Submitted April 2, 2008
Accepted July 14, 2008
Differential pattern of CD4+ and CD8+ T cell immunity to MAGE-A1/A2/A3 in patients with monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma
Oliver Charles Goodyear*, Guy Pratt, Andrew McLarnon, Mark Cook, Karen Piper, and Paul Moss
CR-UK Institute for Cancer Studies, University of Birmingham, Birmingham, West Midlands, United Kingdom
Department of Haematology, University Hospital Birmingham NHS Trust, Edgebaston, Birmingham, United Kingdom
* Corresponding author; email: goodyeoc{at}bham.ac.uk.
The factors that determine progression from monoclonal gammopathy of undetermined significance (MGUS) to multiple myeloma are unclear but may include the breakdown of immune surveillance. Cancer testis antigens (CTAg) are expressed by the majority of myelomas and MGUS tumours and are a potential immune target. We have characterised CD4+ and CD8+ T cell immune responses to MAGE-A1/A2/A3 in these patients. CD4+ T cell immunity to MAGE proteins is stronger and more frequent in MGUS compared to myeloma with a predominantly CD45RA-CCR7- effector memory profile and cytotoxicity against MAGE-positive cell lines. In contrast CD8+ T cell immune responses were present almost exclusively in patients with multiple myeloma, correlating with disease, with a CD45RA+CCR7- memory phenotype, localising poorly to the bone marrow but were able to lyze myeloma cell lines in vitro. This suggests that the CD4+ CTAg-specific immune response may play a role in controlling tumour growth whereas the efficacy of the CD8+ T cell response appears to be limited in vivo. Despite this, patients with evidence of a CTAg-specific immune response had a 53% reduction in mortality over a median follow up of 4 years. These findings have important implications for clinical approaches to CTAg-specific immunotherapy in patients with cancer.
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