期刊
ONCOIMMUNOLOGY
卷 1, 期 4, 页码 -出版社
TAYLOR & FRANCIS INC
DOI: 10.4161/onci.18851
关键词
tumor immunology; TIL therapy; high throughput screening; pMHC multiplexing; T-cell reactivity
资金
- Melanoma Research Alliance [105636]
- CTMM [04I-301]
- Dutch Cancer Society [2009-4282]
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.
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