TIL therapy broadens the tumor-reactive CD8(+) T cell compartment in melanoma patients
Pia Kvistborg, Chengyi Jenny Shu, Bianca Heemskerk, Manuel Fankhauser, Charlotte Albæk Thrue, Mireille Toebes, Nienke van Rooij, Carsten Linnemann, Marit M van Buuren, Jos H M Urbanus, Joost B Beltman, Per Thor Straten, Yong F Li, Paul F Robbins, Michal J Besser, Jacob Schachter, Gemma G Kenter, Mark E Dudley, Steven A Rosenberg, John B A G Haanen, Sine Reker Hadrup, Ton N M Schumacher, Pia Kvistborg, Chengyi Jenny Shu, Bianca Heemskerk, Manuel Fankhauser, Charlotte Albæk Thrue, Mireille Toebes, Nienke van Rooij, Carsten Linnemann, Marit M van Buuren, Jos H M Urbanus, Joost B Beltman, Per Thor Straten, Yong F Li, Paul F Robbins, Michal J Besser, Jacob Schachter, Gemma G Kenter, Mark E Dudley, Steven A Rosenberg, John B A G Haanen, Sine Reker Hadrup, Ton N M Schumacher
Abstract
There is strong evidence that both adoptive T cell transfer and T cell checkpoint blockade can lead to regression of human melanoma. However, little data are available on the effect of these cancer therapies on the tumor-reactive T cell compartment. To address this issue we have profiled therapy-induced T cell reactivity against a panel of 145 melanoma-associated CD8(+) T cell epitopes. Using this approach, we demonstrate that individual tumor-infiltrating lymphocyte cell products from melanoma patients contain unique patterns of reactivity against shared melanoma-associated antigens, and that the combined magnitude of these responses is surprisingly low. Importantly, TIL therapy increases the breadth of the tumor-reactive T cell compartment in vivo, and T cell reactivity observed post-therapy can almost in full be explained by the reactivity observed within the matched cell product. These results establish the value of high-throughput monitoring for the analysis of immuno-active therapeutics and suggest that the clinical efficacy of TIL therapy can be enhanced by the preparation of more defined tumor-reactive T cell products.
Figures
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Source: PubMed