Abstract

Melanoma-associated Ag (MAGE)-C2, an immunogenic cancer germline (testis) Ag, is highly expressed by various tumor cells, thymic medullary epithelial cells, and germ cells. In this study, we aimed to explore the immunologic properties of MAGE-C2–specific CD8+ T cells and the relationship of its TCR β-chain V region (TCR vβ) subfamily distribution to prognosis of patients with esophageal cancer. PBMCs and tumor-infiltrating lymphocytes expanded by CD3/CD28 Dynabeads and MAGE-C2 peptides in vitro resulted in the induction of lysosome-associated membrane protein-1 (LAMP-1 or CD107a) on the cell surface and the production of IFN-γ by MAGE-C2–specific CD8+ T cells. We found differential TCR vβ subfamily distribution among flow-sorted CD107a+IFN-γ+ and CD107a−IFN-γ− CD8+ T cells. The proportion of CD107a+ and/or IFN-γ+ tetramer+ CD8+ T cells was lower in patients with lymph node metastasis, late tumor stage, and poorly differentiated state (p < 0.05). T-box transcription factor was positively correlated with CD107a and IFN-γ. Kaplan–Meier analysis showed that patients whose MAGE-C2–specific CD8+ T cells expressed high CD107a and/or IFN-γ had a longer survival time when compared with patients whose MAGE-C2–specific CD8+ T cells expressed low levels of CD107a and/or IFN-γ. Moreover, analysis of TCR vβ subfamily distribution revealed that a higher frequency of TCR vβ16 in MAGE-C2–specific CD8+ T cells was positively correlated with a better prognosis. These results suggest that the presence of functional MAGE-C2–specific CD8+ T cells had an independent prognostic impact on the survival of patients with esophageal cancer.

Footnotes

This work was supported by National Natural Science Foundation of China Grants 81171986 and 81702810.

Conception and design, P.L., X.C., and Y.Z.; development of methodology, Y.Z., X.C., and Y.P; acquisition of data (e.g., provided animals, acquired and managed patients, provided facilities), P.L., X.C., G.Q., L.H., Y.Z., and L.W.; analysis and interpretation of data (e.g., statistical analysis, biostatistics, and computational analysis), P.L., X.C., Y.Z., Y.P., Q.Z., Z.Z., and H.C; writing, review, and/or revision of the manuscript, P.L., X.C., and Y.Z.; study supervision, Y.Z. and S.Y. P.L., X.C., and Y.Z. had full access to all data and take responsibility for the integrity and accuracy of the data analysis.

The online version of this article contains supplemental material.

Abbreviations used in this article:

CTAcancer germline (testis) AgDCdendritic cellESCAesophageal cancerESCCesophageal squamous cell carcinomaMAGEmelanoma-associated AgqRT-PCRquantitative RT-PCRRNA-seqRNA sequencingTCGAThe Cancer Genome AtlasTCR vβTCR β-chain V regionTILtumor-infiltrating lymphocyteReceived December 27, 2021.Accepted July 8, 2022.Copyright © 2022 by The American Association of Immunologists, Inc.