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

Abstract

Increased numbers of CD8⁺CD28^neg. 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⁺CD28^neg. 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 CD28^neg. T cells in a melanoma patient with recurrent disease who achieved long-term disease-free status. As a result, the patient's oligoclonal CD8⁺CD28^neg. 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⁺CD28^neg. T cells expressed a cytotoxicity marker, CD57, only 0.01% of CD8⁺ CD28^neg. 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 CD28^neg. compartment of the immunological memory. Since the patient is in ongoing complete remission for more than 9 years, CD8⁺CD28^neg. T cells with the Melan-A-specific TCR might contribute to antitumor immunity in this patient.

Keywords: Antitumoral T cell memory; CD28− T lymphocytes; Melan-A; Melanoma; Public TCR; Self-specific public TCR.