Spontaneous CD4(+) and CD8(+) T-cell responses directed against cancer testis antigens are present in the peripheral blood of testicular cancer patients
Research output: Contribution to journal › Article › peer-review
- School Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, University of Birmingham.
- University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
Cancer/testis antigen (CTAg) expression is restricted to spermatogenic cells in an immune-privileged site within the testis. However, these proteins are expressed aberrantly by malignant cells and T-cell responses against CTAgs develop in many cancer patients. We investigated the prevalence, magnitude and phenotype of CTAg-specific T cells in the blood of patients with testicular germ cell tumors (TGCTs). CD8(+) and CD4(+) T-cell responses against MAGE-A family antigens were present in 44% (20/45) of patients' samples assayed by ex vivo IFN-γ ELISPOT. The presence of MAGE-specific CD8(+) T cells was further determined following short-term in vitro expansion through the use of pMHC-I multimers containing known immunogenic peptides. Longitudinal analysis revealed that the frequency of MAGE-specific T cells decreased by 89% following orchidectomy suggesting that persistence of tumor antigen is required to sustain CTAg-specific T-cell immunity. Notably, this decrease correlated with a decline in the global effector/memory T-cell pool following treatment. Spontaneous T-cell immunity against CTAg proteins therefore develops in many patients with testicular cancer and may play an important role in the excellent clinical outcome of patients with this tumor subtype.
|Number of pages||11|
|Journal||European Journal of Immunology|
|Early online date||28 May 2017|
|Publication status||Published - Jul 2017|
- Testicular cancer, Tumor immunology, Cancer testis antigens, MAGE, T cells