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Predicting the response to CTLA-4 blockade by longitudinal noninvasive monitoring of CD8 T cells
Immunotherapy using checkpoint-blocking antibodies against targets such as CTLA-4 and PD-1 can cure melanoma and non–small cell lung cancer in a subset of patients. The presence of CD8 T cells in the tumor correlates with improved survival. We show that immuno–positron emission tomography (immuno-PE...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5551571/ https://www.ncbi.nlm.nih.gov/pubmed/28666979 http://dx.doi.org/10.1084/jem.20161950 |
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author | Rashidian, Mohammad Ingram, Jessica R. Dougan, Michael Dongre, Anushka Whang, Katherine A. LeGall, Camille Cragnolini, Juan J. Bierie, Brian Gostissa, Monica Gorman, James Grotenbreg, Gijsbert M. Bhan, Atul Weinberg, Robert A. Ploegh, Hidde L. |
author_facet | Rashidian, Mohammad Ingram, Jessica R. Dougan, Michael Dongre, Anushka Whang, Katherine A. LeGall, Camille Cragnolini, Juan J. Bierie, Brian Gostissa, Monica Gorman, James Grotenbreg, Gijsbert M. Bhan, Atul Weinberg, Robert A. Ploegh, Hidde L. |
author_sort | Rashidian, Mohammad |
collection | PubMed |
description | Immunotherapy using checkpoint-blocking antibodies against targets such as CTLA-4 and PD-1 can cure melanoma and non–small cell lung cancer in a subset of patients. The presence of CD8 T cells in the tumor correlates with improved survival. We show that immuno–positron emission tomography (immuno-PET) can visualize tumors by detecting infiltrating lymphocytes and, through longitudinal observation of individual animals, distinguish responding tumors from those that do not respond to therapy. We used (89)Zr-labeled PEGylated single-domain antibody fragments (VHHs) specific for CD8 to track the presence of intratumoral CD8(+) T cells in the immunotherapy-susceptible B16 melanoma model in response to checkpoint blockade. A (89)Zr-labeled PEGylated anti-CD8 VHH detected thymus and secondary lymphoid structures as well as intratumoral CD8 T cells. Animals that responded to CTLA-4 therapy showed a homogeneous distribution of the anti-CD8 PET signal throughout the tumor, whereas more heterogeneous infiltration of CD8 T cells correlated with faster tumor growth and worse responses. To support the validity of these observations, we used two different transplantable breast cancer models, yielding results that conformed with predictions based on the antimelanoma response. It may thus be possible to use immuno-PET and monitor antitumor immune responses as a prognostic tool to predict patient responses to checkpoint therapies. |
format | Online Article Text |
id | pubmed-5551571 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-55515712018-02-07 Predicting the response to CTLA-4 blockade by longitudinal noninvasive monitoring of CD8 T cells Rashidian, Mohammad Ingram, Jessica R. Dougan, Michael Dongre, Anushka Whang, Katherine A. LeGall, Camille Cragnolini, Juan J. Bierie, Brian Gostissa, Monica Gorman, James Grotenbreg, Gijsbert M. Bhan, Atul Weinberg, Robert A. Ploegh, Hidde L. J Exp Med Research Articles Immunotherapy using checkpoint-blocking antibodies against targets such as CTLA-4 and PD-1 can cure melanoma and non–small cell lung cancer in a subset of patients. The presence of CD8 T cells in the tumor correlates with improved survival. We show that immuno–positron emission tomography (immuno-PET) can visualize tumors by detecting infiltrating lymphocytes and, through longitudinal observation of individual animals, distinguish responding tumors from those that do not respond to therapy. We used (89)Zr-labeled PEGylated single-domain antibody fragments (VHHs) specific for CD8 to track the presence of intratumoral CD8(+) T cells in the immunotherapy-susceptible B16 melanoma model in response to checkpoint blockade. A (89)Zr-labeled PEGylated anti-CD8 VHH detected thymus and secondary lymphoid structures as well as intratumoral CD8 T cells. Animals that responded to CTLA-4 therapy showed a homogeneous distribution of the anti-CD8 PET signal throughout the tumor, whereas more heterogeneous infiltration of CD8 T cells correlated with faster tumor growth and worse responses. To support the validity of these observations, we used two different transplantable breast cancer models, yielding results that conformed with predictions based on the antimelanoma response. It may thus be possible to use immuno-PET and monitor antitumor immune responses as a prognostic tool to predict patient responses to checkpoint therapies. The Rockefeller University Press 2017-08-07 /pmc/articles/PMC5551571/ /pubmed/28666979 http://dx.doi.org/10.1084/jem.20161950 Text en © 2017 Rashidian et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Research Articles Rashidian, Mohammad Ingram, Jessica R. Dougan, Michael Dongre, Anushka Whang, Katherine A. LeGall, Camille Cragnolini, Juan J. Bierie, Brian Gostissa, Monica Gorman, James Grotenbreg, Gijsbert M. Bhan, Atul Weinberg, Robert A. Ploegh, Hidde L. Predicting the response to CTLA-4 blockade by longitudinal noninvasive monitoring of CD8 T cells |
title | Predicting the response to CTLA-4 blockade by longitudinal noninvasive monitoring of CD8 T cells |
title_full | Predicting the response to CTLA-4 blockade by longitudinal noninvasive monitoring of CD8 T cells |
title_fullStr | Predicting the response to CTLA-4 blockade by longitudinal noninvasive monitoring of CD8 T cells |
title_full_unstemmed | Predicting the response to CTLA-4 blockade by longitudinal noninvasive monitoring of CD8 T cells |
title_short | Predicting the response to CTLA-4 blockade by longitudinal noninvasive monitoring of CD8 T cells |
title_sort | predicting the response to ctla-4 blockade by longitudinal noninvasive monitoring of cd8 t cells |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5551571/ https://www.ncbi.nlm.nih.gov/pubmed/28666979 http://dx.doi.org/10.1084/jem.20161950 |
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