Abstract
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.
Highlights
Testicular cancer is the most common tumor among young men of 20–34 years of age and is increasing in incidence [1]
We find that strong CD8+ and CD4+ CTAgspecific T-cell responses are found in many patients and that the global memory T-cell pool is substantially increased at diagnosis
peripheral blood mononuclear cells (PBMCs) were stimulated with overlapping peptide pools derived from Cancer/testis antigen (CTAg) proteins prior to analysis using IFN-γ ELISPOT assay
Summary
Testicular cancer is the most common tumor among young men of 20–34 years of age and is increasing in incidence [1]. Cancer/testis antigens (CTAg) are proteins that are expressed in germ cells but are usually silenced in somatic cells [6]. They include the melanoma-associated antigen (MAGE) family and NYESO-1 antigen which are attractive candidates for cancer vaccine trials and adoptive cellular immunotherapy [7,8,9]. The magnitude of CTAg-specific responses decreases substantially after treatment and coincides with a reduction in the T-cell memory pool These data indicate that natural CTAgspecific immunity is established in many patients with testicular cancer and comprises a population of short-lived effector T cells that persist poorly in the absence of antigen
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