Kvistborg, Pia2; Shu, Chengyi Jenny2; Heemskerk, Bianca2; Fankhauser, Manuel2; Thrue, Charlotte Albæk1; Toebes, Mireille2; van Rooij, Nienke2; Linnemann, Carsten2; van Buuren, Marit M2; Urbanus, Jos H M2; Beltman, Joost B2; thor Straten, Per1; Li, Yong F2; Robbins, Paul F2; Besser, Michal J2; Schachter, Jacob2; Kenter, Gemma G2; Dudley, Mark E2; Rosenberg, Steven A2; Haanen, John B A G2; Hadrup, Sine Reker1; Schumacher, Ton N M2
1 Department of Haematology, Herlev and Gentofte Hospital, The Capital Region of Denmark2 unknown
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.