Immunitrack co-authors Nature paper on in depth T cell profile study, in melanoma cancer patients
Immunitrack is proud to have contributed to this very comprehensive study on T cell profiling in melanoma patients, that was recently published in Nature. The study elucidates the relationship between TCR specificity and T cell phenotype, and by using our NeoScreen platform, we contributed to the investigation by performing in vitro HLA/epitope binding studies that were correlated with TCR avidity measurements. Our experiments showed that the TCR avidity was proportional to the affinity of the HLA/epitope complexes. Furthermore, we demonstrated how the exact position of the mutated residue within neoantigens affects the affinities and stabilities of HLA/epitope complexes and thereby the TCR avidities.
This study aimed at determining how the target antigen recognition of TCRs is related to the phenotype of T cells.
To investigate this, Oliviera et al. obtained tumor-infiltrating and peripheral T cells from melanoma patients and were, through a series of sophisticated methods, able to show that tumour specificity shapes the phenotype of tumour-infiltrating CD8+ T cells.
Their results demonstrate that TCRs recognizing over-expressed shared melanoma antigens often have a low avidity, and that T cells expressing these TCRs have a more exhausted phenotype than non-tumour reactive T cells with viral antigen-specific TCRs. Furthermore, the circulating level of exhausted tumor-reactive T cells was found to be increased in patients with a poor response to immune checkpoint blockade.
Overall, this study sheds new light on the mechanisms behind T cell exhaustion and delivered an unambiguous definition of antigen specificities, phenotypes and dynamics of tumour-specific CD8+ T cells in melanoma.
The results were recently published in Nature journal ▸