Fine analysis of spontaneous MAGE-C1/CT7–specific immunity in melanoma patients

Abstract

Cancer/testis (CT) antigens represent prime candidates for immunotherapy in cancer patients, because their expression is restricted to cancer cells and germ cells of the testis. MAGE-C1/CT7 is a CT antigen that is highly expressed in several types of cancers. Spontaneous occurrence of CT7-specific antibodies was previously detected by SEREX screen in a melanoma patient. However, naturally occurring CT7-specific T-cell responses have thus far not been detected. Peripheral blood mononuclear cells (PBMCs) from 26 metastatic melanoma patients expressing CT7 in their tumor lesions (CT7 + ) were analyzed for CT7-specific T-cell responses using overlapping peptides. CT7-specific CD4 + T-cell responses were detected in three patients (11.5%). These CT7-specific CD4 + T-cell responses were detectable in melanoma patients' PBMCs exclusively from preexisting CD45RA − memory CD4 + T-cell pool. Additional CT7-specific memory CD4 + T-cell responses were detected in CT7 + melanoma patients after depletion of CD4 + CD25high Treg cells showing that Treg cells impact on CT7-specific CD4 + T cells in melanoma patients. CT7-specific CD4 + T-cell clones were generated and used to define minimal epitopes, restriction elements, and confirm the recognition of naturally processed antigen. Surprisingly, these clones were able to secrete perforin and exert cytotoxicity. This study shows that CT7 can induce specific cellular immunity in melanoma patients. Based on these findings, CT7 will be further explored as a potential vaccine for melanoma immunotherapy.cancer/testis antigens | T-cell response

Identification and translational validation of novel mammaglobin-A CD8 T cell epitopes

“…These studies confirm and extend the results of Bharat et al, who demonstrated pre-existing CD8 T cell responses to the MAM-A2.1 epitope in breast cancer patients by tetramer and ELISPOT analysis [2]. Pre-existing CD8 T cell responses to shared tumor antigens have been previously described in melanoma patients [3, 11, 20, 26], and for the shared tumor antigens HER2 [8] and NY-ESO-1 [16]. Immunohistochemistry studies in breast and other solid malignancies [1] now suggest that endogenous antitumor CD8 T cell responses are associated with a favorable prognosis [3].…”

Spontaneous Peripheral T-cell Responses toward the Tumor-Associated Antigen Cyclin D1 in Patients with Clear Cell Renal Cell Carcinoma

“…T-cell stimulation was conducted as described previously (10). Briefly, CD8 þ and CD4 þ T cells were isolated sequentially from PBMCs by positive selection using MACS (Miltenyi Biotech) according to the manufacturer's instructions.…”

Hypomethylation of Alu repetitive elements in esophageal mucosa, and its potential contribution to the epigenetic field for cancerization

“…''Normally methylated'' genes are physiologically methylated and unexpressed in most tissues of adults, except testicular germ cells. In contrast, they are demethylated and expressed in various types of human cancers [21], and specific ones, such as NY-ESO-1 and MAGE-C1, are expected to be useful as potential targets for cancer immunotherapy [22,23]. The presence of global hypomethylation is associated with increased rates of chromosome recombination and increased incidence of tumor formation [24][25][26].…”