TIL therapy broadens the tumor-reactive CD8+ T cell compartment in melanoma patients

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-ind...

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Veröffentlicht in:Oncoimmunology Jg. 1; H. 4; S. 409 - 418
Hauptverfasser: Kvistborg, Pia, Shu, Chengyi Jenny, Heemskerk, Bianca, Fankhauser, Manuel, Thrue, Charlotte Albæk, Toebes, Mireille, van Rooij, Nienke, Linnemann, Carsten, van Buuren, Marit M., Urbanus, Jos H.M., Beltman, Joost B., thor Straten, Per, Li, Yong F., Robbins, Paul F., Besser, Michal J., Schachter, Jacob, Kenter, Gemma G., Dudley, Mark E., Rosenberg, Steven A., Haanen, John B.A.G., Hadrup, Sine Reker, Schumacher, Ton N.M.
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States Taylor & Francis 01.07.2012
Landes Bioscience
Schlagworte:
Binding
Biology
Bioscience
Calcium
Cancer
Cell
Cycle
high throughput screening
Landes
Organogenesis
pMHC multiplexing
Proteins
Research Paper
T-cell reactivity
TIL therapy
tumor immunology
ISSN:2162-4011, 2162-402X, 2162-402X
Online-Zugang:Volltext
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Zusammenfassung: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.
Bibliographie:ObjectType-Article-1
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These authors contributed equally to this work.
ISSN:2162-4011
2162-402X
2162-402X
DOI:10.4161/onci.18851