In this Timeline, we describe the characteristics of tumour antigens that are recognized by spontaneous T cell responses in cancer patients and the paths that led to their identification. We explain on what genetic basis most, but not all, of these antigens are tumour specific: that is, present on tumour cells but not on normal cells. We also discuss how strategies that target these tumour-specific antigens can lead either to tumour-specific or to crossreactive T cell responses, which is an issue that has important safety implications in immunotherapy. These safety issues are even more of a concern for strategies targeting antigens that are not known to induce spontaneous T cell responses in patients.
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The authors thank S. Depelchin and J. Klein for editorial work, and D. Godelaine and A. Van Pel for reviewing the manuscript.
Patents on human tumour antigens owned by the Ludwig Institute. Part of licence fees. P.G.C., T.B., B.J.V and P.V.
- Adoptive transfer
In cancer immunotherapy, the infusion into patients of autologous antitumour T cells that have been amplified in vitro. The lymphocytes can also be transduced with retroviral expression vectors in order to express a given T cell receptor or other gene products.
Hyporesponsiveness or unresponsiveness of T lymphocytes after recognition of their antigen.
- Central tolerance
The deletion or inactivation of immature autoreactive B cells and T cells of the primary lymphoid organs: the bone marrow (B cells) and the thymus (T cells). The remaining mature autoreactive B cells and T cells are dealt with by the mechanisms of peripheral tolerance.
The removal of an amide group. In N-glycosylated proteins, deglycosylation of an asparagine by the peptide N-glycanase generates an aspartate by deamidation. This can result in an antigenic peptide.
The molecular configuration of a peptide that is recognized by a T cell receptor or by an antibody.
The elimination of lymphocytes by a combination of lymphocyte-depleting chemotherapy (cyclophosphamide and fludarabine) and total body irradiation.
- Serological analysis of recombinant cDNA expression libraries
(SEREX). A procedure whereby proteins from human tumours are screened for recognition by autologous serum.
- Thymic epithelial cells
The thymus contains developing T lymphocytes and a stroma that consists of epithelial cells and dendritic cells. Epithelial cells of the thymic medulla, in which the transcription factor autoimmune regulator controls the expression of peripheral tissue antigens, contribute to the induction of central tolerance for T lymphocytes.
Inflammation of the uvea, which is the middle layer of the eye, between the retina and the sclera.
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Coulie, P., Van den Eynde, B., van der Bruggen, P. et al. Tumour antigens recognized by T lymphocytes: at the core of cancer immunotherapy. Nat Rev Cancer 14, 135–146 (2014). https://doi.org/10.1038/nrc3670
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