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

Pia Kvistborg, Chengyi Jenny Shu, Bianca Heemskerk, Manuel Fankhauser, Charlotte Albaek 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. HaanenSine Reker Hadrup, Ton N. M. Schumacher

Research output: Contribution to journalJournal articleResearchpeer-review


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.
Original languageEnglish
Issue number4
Pages (from-to)409-418
Publication statusPublished - 2012
Externally publishedYes


  • Immunology and Allergy
  • Oncology
  • Immunology
  • High throughput screening
  • PMHC multiplexing
  • T-cell reactivity
  • TIL therapy
  • Tumor immunology
  • cyclin dependent kinase 4
  • epitope
  • gamma interferon
  • HLA A2 antigen
  • melan A
  • melanoma antigen
  • meloe 1 antigen
  • NY ESO 1 antigen
  • survivin
  • unclassified drug
  • allele
  • antigen expression
  • antigen recognition
  • article
  • cancer immunotherapy
  • CD8+ T lymphocyte
  • CD8+ T lymphocyte profiling
  • cellular immunity
  • controlled study
  • cytokine production
  • human
  • human cell
  • human tissue
  • immunoreactivity
  • in vivo study
  • investigative procedures
  • lymphocyte subpopulation
  • melanoma
  • peripheral blood mononuclear cell
  • predictive value
  • priority journal
  • treatment response
  • tumor infiltrating T lymphocyte therapy
  • tumor immunology
  • high throughput screening
  • pMHC multiplexing
  • Primates Mammalia Vertebrata Chordata Animalia (Animals, Chordates, Humans, Mammals, Primates, Vertebrates) - Hominidae [86215] human common
  • melanoma-associated antigen
  • 02506, Cytology - Animal
  • 02508, Cytology - Human
  • 15002, Blood - Blood and lymph studies
  • 15004, Blood - Blood cell studies
  • 18506, Integumentary system - Pathology
  • 24003, Neoplasms - Immunology
  • 24004, Neoplasms - Pathology, clinical aspects and systemic effects
  • 34502, Immunology - General and methods
  • 34508, Immunology - Immunopathology, tissue immunology
  • Clinical Immunology
  • Dermatology
  • Methods and Techniques
  • melanoma Melanoma (MeSH) neoplastic disease, integumentary system disease
  • cell reactivity
  • Human Medicine, Medical Sciences
  • CD8-positive T cell immune system, blood and lymphatics
  • high-throughput monitoring laboratory techniques, genetic techniques
  • tumor-infiltrating lymphocyte therapy TIL therapy therapeutic and prophylactic techniques, clinical techniques


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