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Erschienen in: Immunologic Research 1/2018

14.11.2017 | Original Article

CD28neg. T lymphocytes of a melanoma patient harbor tumor immunity and a high frequency of germline-encoded and public TCRs

verfasst von: Hisayoshi Hashimoto, Marco Sterk, Karin Schilbach

Erschienen in: Immunologic Research | Ausgabe 1/2018

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Abstract

Increased numbers of CD8+CD28neg. T cells have been detected in the peripheral blood of patients with several types of malignancies. However, the role of these cells in anticancer immunity are not yet clear and CD8+CD28neg. T cells are a controversially discussed subpopulation reported both as immunosuppressive and cytotoxic. In this study, we examined the T cell receptor (TCR) repertoire and complementarity-determining region 3 sequences of CD28neg. T cells in a melanoma patient with recurrent disease who achieved long-term disease-free status. As a result, the patient’s oligoclonal CD8+CD28neg. T cell compartment holds TCRs that are public and specific for Melan-A as well as several public TCRs reported for common viral antigens. While over 80% of his CD8+CD28neg. T cells expressed a cytotoxicity marker, CD57, only 0.01% of CD8+ CD28neg. T cells were positive for Foxp3. In conclusion, our results demonstrate that besides virus-specific also tumor-associated self-antigen targeting T cells accumulate in the CD28neg. compartment of the immunological memory. Since the patient is in ongoing complete remission for more than 9 years, CD8+CD28neg. T cells with the Melan-A-specific TCR might contribute to antitumor immunity in this patient.
Literatur
6.
Zurück zum Zitat Azuma M, Phillips JH, Lanier LL. CD28- T lymphocytes. Antigenic and functional properties. J Immunol. 1993;150(4):1147–59.PubMed Azuma M, Phillips JH, Lanier LL. CD28- T lymphocytes. Antigenic and functional properties. J Immunol. 1993;150(4):1147–59.PubMed
7.
Zurück zum Zitat Ciubotariu R, Colovai AI, Pennesi G, Liu Z, Smith D, Berlocco P, et al. Specific suppression of human CD4+ Th cell responses to pig MHC antigens by CD8+CD28- regulatory T cells. J Immunol. 1998;161(10):5193–202.PubMed Ciubotariu R, Colovai AI, Pennesi G, Liu Z, Smith D, Berlocco P, et al. Specific suppression of human CD4+ Th cell responses to pig MHC antigens by CD8+CD28- regulatory T cells. J Immunol. 1998;161(10):5193–202.PubMed
13.
Zurück zum Zitat Urbaniak-Kujda D, Kapelko-Słowik K, Wołowiec D, Dybko J, Hałoń A, Jaźwiec B, et al. Increased percentage of CD8+CD28- suppressor lymphocytes in peripheral blood and skin infiltrates correlates with advanced disease in patients with cutaneous T-cell lymphomas. Postepy Hig Med Dosw (Online). 2009;63:355–9. Urbaniak-Kujda D, Kapelko-Słowik K, Wołowiec D, Dybko J, Hałoń A, Jaźwiec B, et al. Increased percentage of CD8+CD28- suppressor lymphocytes in peripheral blood and skin infiltrates correlates with advanced disease in patients with cutaneous T-cell lymphomas. Postepy Hig Med Dosw (Online). 2009;63:355–9.
14.
Zurück zum Zitat Gruber IV, el Yousfi S, Dürr-Störzer S, Wallwiener D, Solomayer EF, Fehm T. Down-regulation of CD28, TCR-zeta (zeta) and up-regulation of FAS in peripheral cytotoxic T-cells of primary breast cancer patients. Anticancer Res. 2008;28(2a):779–84.PubMed Gruber IV, el Yousfi S, Dürr-Störzer S, Wallwiener D, Solomayer EF, Fehm T. Down-regulation of CD28, TCR-zeta (zeta) and up-regulation of FAS in peripheral cytotoxic T-cells of primary breast cancer patients. Anticancer Res. 2008;28(2a):779–84.PubMed
20.
24.
35.
Zurück zum Zitat Weekes MP, Carmichael AJ, Wills MR, Mynard K, Sissons JG. Human CD28-CD8+ T cells contain greatly expanded functional virus-specific memory CTL clones. J Immunol. 1999;162(12):7569–77.PubMed Weekes MP, Carmichael AJ, Wills MR, Mynard K, Sissons JG. Human CD28-CD8+ T cells contain greatly expanded functional virus-specific memory CTL clones. J Immunol. 1999;162(12):7569–77.PubMed
38.
Zurück zum Zitat Hirokawa M, Horiuchi T, Kawabata Y, Kitabayashi A, Saitoh H, Ichikawa Y, et al. Oligoclonal expansion of CD4(+)CD28(−) T lymphocytes in recipients of allogeneic hematopoietic cell grafts and identification of the same T cell clones within both CD4(+)CD28(+) and CD4(+)CD28(−) T cell subsets. Bone Marrow Transplant. 2001;27(10):1095–100. https://doi.org/10.1038/sj.bmt.1703045.CrossRefPubMed Hirokawa M, Horiuchi T, Kawabata Y, Kitabayashi A, Saitoh H, Ichikawa Y, et al. Oligoclonal expansion of CD4(+)CD28(−) T lymphocytes in recipients of allogeneic hematopoietic cell grafts and identification of the same T cell clones within both CD4(+)CD28(+) and CD4(+)CD28(−) T cell subsets. Bone Marrow Transplant. 2001;27(10):1095–100. https://​doi.​org/​10.​1038/​sj.​bmt.​1703045.CrossRefPubMed
39.
Zurück zum Zitat Horiuchi T, Hirokawa M, Kawabata Y, Kitabayashi A, Matsutani T, Yoshioka T, et al. Identification of the T cell clones expanding within both CD8(+)CD28(+) and CD8(+)CD28(−) T cell subsets in recipients of allogeneic hematopoietic cell grafts and its implication in post-transplant skewing of T cell receptor repertoire. Bone Marrow Transplant. 2001;27(7):731–9. https://doi.org/10.1038/sj.bmt.1702859.CrossRefPubMed Horiuchi T, Hirokawa M, Kawabata Y, Kitabayashi A, Matsutani T, Yoshioka T, et al. Identification of the T cell clones expanding within both CD8(+)CD28(+) and CD8(+)CD28(−) T cell subsets in recipients of allogeneic hematopoietic cell grafts and its implication in post-transplant skewing of T cell receptor repertoire. Bone Marrow Transplant. 2001;27(7):731–9. https://​doi.​org/​10.​1038/​sj.​bmt.​1702859.CrossRefPubMed
Metadaten
Titel
CD28neg. T lymphocytes of a melanoma patient harbor tumor immunity and a high frequency of germline-encoded and public TCRs
verfasst von
Hisayoshi Hashimoto
Marco Sterk
Karin Schilbach
Publikationsdatum
14.11.2017
Verlag
Springer US
Erschienen in
Immunologic Research / Ausgabe 1/2018
Print ISSN: 0257-277X
Elektronische ISSN: 1559-0755
DOI
https://doi.org/10.1007/s12026-017-8976-1

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