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. Haanen; Sine Reker Hadrup; Ton N. M. Schumacher

doi:10.4161/onci.18851

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 journal › Journal article › Research › peer-review

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.

Original language	English
Journal	OncoImmunology
Volume	1
Issue number	4
Pages (from-to)	409-418
ISSN	2162-4011
DOIs	https://doi.org/10.4161/onci.18851
Publication status	Published - 2012
Externally published	Yes

Keywords

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
ONCOLOGY
IMMUNOLOGY
METASTATIC MELANOMA
INFILTRATING LYMPHOCYTES
ADOPTIVE TRANSFER
RESPONSES
CANCER
TRANSPLANTATION
IMMUNOTHERAPY
GENERATION
MUTATION
DESIGN
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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.4161/onci.18851

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Kvistborg, P., Shu, C. J., Heemskerk, B., Fankhauser, M., Thrue, C. A., Toebes, M., van Rooij, N., Linnemann, C., van Buuren, M. M., Urbanus, J. H. M., Beltman, J. B., Straten, P. T., Li, Y. F., Robbins, P. F., Besser, M. J., Schachter, J., Kenter, G. G., Dudley, M. E., Rosenberg, S. A., ... Schumacher, T. N. M. (2012). TIL therapy broadens the tumor-reactive CD8(+) T cell compartment in melanoma patients. OncoImmunology, 1(4), 409-418. https://doi.org/10.4161/onci.18851

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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.",

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author = "Pia Kvistborg and Shu, {Chengyi Jenny} and Bianca Heemskerk and Manuel Fankhauser and Thrue, {Charlotte Albaek} and Mireille Toebes and {van Rooij}, Nienke and Carsten Linnemann and {van Buuren}, {Marit M.} and Urbanus, {Jos H. M.} and Beltman, {Joost B.} and Straten, {Per Thor} and Li, {Yong F.} and Robbins, {Paul F.} and Besser, {Michal J.} and Jacob Schachter and Kenter, {Gemma G.} and Dudley, {Mark E.} and Rosenberg, {Steven A.} and Haanen, {John B. A. G.} and Hadrup, {Sine Reker} and Schumacher, {Ton N. M.}",

year = "2012",

doi = "10.4161/onci.18851",

language = "English",

volume = "1",

pages = "409--418",

journal = "OncoImmunology",

issn = "2162-4011",

publisher = "Taylor & Francis Inc.",

number = "4",

}

Kvistborg, P, Shu, CJ, Heemskerk, B, Fankhauser, M, Thrue, CA, Toebes, M, van Rooij, N, Linnemann, C, van Buuren, MM, Urbanus, JHM, Beltman, JB, Straten, PT, Li, YF, Robbins, PF, Besser, MJ, Schachter, J, Kenter, GG, Dudley, ME, Rosenberg, SA, Haanen, JBAG, Hadrup, SR & Schumacher, TNM 2012, 'TIL therapy broadens the tumor-reactive CD8(+) T cell compartment in melanoma patients', OncoImmunology, vol. 1, no. 4, pp. 409-418. https://doi.org/10.4161/onci.18851

TY - JOUR

T1 - TIL therapy broadens the tumor-reactive CD8(+) T cell compartment in melanoma patients

AU - Kvistborg, Pia

AU - Shu, Chengyi Jenny

AU - Heemskerk, Bianca

AU - Fankhauser, Manuel

AU - Thrue, Charlotte Albaek

AU - Toebes, Mireille

AU - van Rooij, Nienke

AU - Linnemann, Carsten

AU - van Buuren, Marit M.

AU - Urbanus, Jos H. M.

AU - Beltman, Joost B.

AU - Straten, Per Thor

AU - Li, Yong F.

AU - Robbins, Paul F.

AU - Besser, Michal J.

AU - Schachter, Jacob

AU - Kenter, Gemma G.

AU - Dudley, Mark E.

AU - Rosenberg, Steven A.

AU - Haanen, John B. A. G.

AU - Hadrup, Sine Reker

AU - Schumacher, Ton N. M.

PY - 2012

Y1 - 2012

N2 - 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.

AB - 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.

KW - Immunology and Allergy

KW - Oncology

KW - Immunology

KW - High throughput screening

KW - PMHC multiplexing

KW - T-cell reactivity

KW - TIL therapy

KW - Tumor immunology

KW - cyclin dependent kinase 4

KW - epitope

KW - gamma interferon

KW - HLA A2 antigen

KW - melan A

KW - melanoma antigen

KW - meloe 1 antigen

KW - NY ESO 1 antigen

KW - survivin

KW - unclassified drug

KW - allele

KW - antigen expression

KW - antigen recognition

KW - article

KW - cancer immunotherapy

KW - CD8+ T lymphocyte

KW - CD8+ T lymphocyte profiling

KW - cellular immunity

KW - controlled study

KW - cytokine production

KW - human

KW - human cell

KW - human tissue

KW - immunoreactivity

KW - in vivo study

KW - investigative procedures

KW - lymphocyte subpopulation

KW - melanoma

KW - peripheral blood mononuclear cell

KW - predictive value

KW - priority journal

KW - treatment response

KW - tumor infiltrating T lymphocyte therapy

KW - ONCOLOGY

KW - IMMUNOLOGY

KW - METASTATIC MELANOMA

KW - INFILTRATING LYMPHOCYTES

KW - ADOPTIVE TRANSFER

KW - RESPONSES

KW - CANCER

KW - TRANSPLANTATION

KW - IMMUNOTHERAPY

KW - GENERATION

KW - MUTATION

KW - DESIGN

KW - tumor immunology

KW - high throughput screening

KW - pMHC multiplexing

KW - Primates Mammalia Vertebrata Chordata Animalia (Animals, Chordates, Humans, Mammals, Primates, Vertebrates) - Hominidae [86215] human common

KW - melanoma-associated antigen

KW - 02506, Cytology - Animal

KW - 02508, Cytology - Human

KW - 15002, Blood - Blood and lymph studies

KW - 15004, Blood - Blood cell studies

KW - 18506, Integumentary system - Pathology

KW - 24003, Neoplasms - Immunology

KW - 24004, Neoplasms - Pathology, clinical aspects and systemic effects

KW - 34502, Immunology - General and methods

KW - 34508, Immunology - Immunopathology, tissue immunology

KW - Clinical Immunology

KW - Dermatology

KW - Methods and Techniques

KW - melanoma Melanoma (MeSH) neoplastic disease, integumentary system disease

KW - cell reactivity

KW - Human Medicine, Medical Sciences

KW - CD8-positive T cell immune system, blood and lymphatics

KW - high-throughput monitoring laboratory techniques, genetic techniques

KW - tumor-infiltrating lymphocyte therapy TIL therapy therapeutic and prophylactic techniques, clinical techniques

U2 - 10.4161/onci.18851

DO - 10.4161/onci.18851

M3 - Journal article

SN - 2162-4011

VL - 1

SP - 409

EP - 418

JO - OncoImmunology

JF - OncoImmunology

IS - 4

ER -

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

Abstract

Keywords

UN SDGs

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