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VCAM-1 Density and Tumor Perfusion Predict T-cell Infiltration and Treatment Response in Preclinical Models()()

Cancer immunotherapies have demonstrated durable responses in a range of different cancers. However, only a subset of patients responds to these therapies. We set out to test if non-invasive imaging of tumor perfusion and vascular inflammation may be able to explain differences in T-cell infiltratio...

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Autores principales: Riegler, Johannes, Gill, Herman, Ogasawara, Annie, Hedehus, Maj, Javinal, Vincent, Oeh, Jason, Ferl, Gregory Z., Marik, Jan, Williams, Simon, Sampath, Deepak, Schartner, Jill, Carano, Richard A.D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Neoplasia Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6744528/
https://www.ncbi.nlm.nih.gov/pubmed/31521051
http://dx.doi.org/10.1016/j.neo.2019.08.003
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author Riegler, Johannes
Gill, Herman
Ogasawara, Annie
Hedehus, Maj
Javinal, Vincent
Oeh, Jason
Ferl, Gregory Z.
Marik, Jan
Williams, Simon
Sampath, Deepak
Schartner, Jill
Carano, Richard A.D.
author_facet Riegler, Johannes
Gill, Herman
Ogasawara, Annie
Hedehus, Maj
Javinal, Vincent
Oeh, Jason
Ferl, Gregory Z.
Marik, Jan
Williams, Simon
Sampath, Deepak
Schartner, Jill
Carano, Richard A.D.
author_sort Riegler, Johannes
collection PubMed
description Cancer immunotherapies have demonstrated durable responses in a range of different cancers. However, only a subset of patients responds to these therapies. We set out to test if non-invasive imaging of tumor perfusion and vascular inflammation may be able to explain differences in T-cell infiltration in pre-clinical tumor models, relevant for treatment outcomes. Tumor perfusion and vascular cell adhesion molecule (VCAM-1) density were quantified using magnetic resonance imaging (MRI) and correlated with infiltration of adoptively transferred and endogenous T-cells. MRI biomarkers were evaluated for their ability to detect tumor rejection 3 days after T-cell transfer. Baseline levels of these markers were used to assess their ability to predict PD-L1 treatment response. We found correlations between MRI-derived VCAM-1 density and infiltration of endogenous or adoptively transferred T-cells in some preclinical tumor models. Blocking T-cell binding to endothelial cell adhesion molecules (VCAM-1/ICAM) prevented T-cell mediated tumor rejection. Tumor rejection could be detected 3 days after adoptive T-cell transfer prior to tumor volume changes by monitoring the extracellular extravascular volume fraction. Imaging tumor perfusion and VCAM-1 density before treatment initiation was able to predict the response of MC38 tumors to PD-L1 blockade. These results indicate that MRI based assessment of tumor perfusion and VCAM-1 density can inform about the permissibility of the tumor vasculature for T-cell infiltration which may explain some of the observed variance in treatment response for cancer immunotherapies.
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spelling pubmed-67445282019-09-18 VCAM-1 Density and Tumor Perfusion Predict T-cell Infiltration and Treatment Response in Preclinical Models()() Riegler, Johannes Gill, Herman Ogasawara, Annie Hedehus, Maj Javinal, Vincent Oeh, Jason Ferl, Gregory Z. Marik, Jan Williams, Simon Sampath, Deepak Schartner, Jill Carano, Richard A.D. Neoplasia Original article Cancer immunotherapies have demonstrated durable responses in a range of different cancers. However, only a subset of patients responds to these therapies. We set out to test if non-invasive imaging of tumor perfusion and vascular inflammation may be able to explain differences in T-cell infiltration in pre-clinical tumor models, relevant for treatment outcomes. Tumor perfusion and vascular cell adhesion molecule (VCAM-1) density were quantified using magnetic resonance imaging (MRI) and correlated with infiltration of adoptively transferred and endogenous T-cells. MRI biomarkers were evaluated for their ability to detect tumor rejection 3 days after T-cell transfer. Baseline levels of these markers were used to assess their ability to predict PD-L1 treatment response. We found correlations between MRI-derived VCAM-1 density and infiltration of endogenous or adoptively transferred T-cells in some preclinical tumor models. Blocking T-cell binding to endothelial cell adhesion molecules (VCAM-1/ICAM) prevented T-cell mediated tumor rejection. Tumor rejection could be detected 3 days after adoptive T-cell transfer prior to tumor volume changes by monitoring the extracellular extravascular volume fraction. Imaging tumor perfusion and VCAM-1 density before treatment initiation was able to predict the response of MC38 tumors to PD-L1 blockade. These results indicate that MRI based assessment of tumor perfusion and VCAM-1 density can inform about the permissibility of the tumor vasculature for T-cell infiltration which may explain some of the observed variance in treatment response for cancer immunotherapies. Neoplasia Press 2019-09-11 /pmc/articles/PMC6744528/ /pubmed/31521051 http://dx.doi.org/10.1016/j.neo.2019.08.003 Text en © 2019 Neoplasia Press, Inc. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original article
Riegler, Johannes
Gill, Herman
Ogasawara, Annie
Hedehus, Maj
Javinal, Vincent
Oeh, Jason
Ferl, Gregory Z.
Marik, Jan
Williams, Simon
Sampath, Deepak
Schartner, Jill
Carano, Richard A.D.
VCAM-1 Density and Tumor Perfusion Predict T-cell Infiltration and Treatment Response in Preclinical Models()()
title VCAM-1 Density and Tumor Perfusion Predict T-cell Infiltration and Treatment Response in Preclinical Models()()
title_full VCAM-1 Density and Tumor Perfusion Predict T-cell Infiltration and Treatment Response in Preclinical Models()()
title_fullStr VCAM-1 Density and Tumor Perfusion Predict T-cell Infiltration and Treatment Response in Preclinical Models()()
title_full_unstemmed VCAM-1 Density and Tumor Perfusion Predict T-cell Infiltration and Treatment Response in Preclinical Models()()
title_short VCAM-1 Density and Tumor Perfusion Predict T-cell Infiltration and Treatment Response in Preclinical Models()()
title_sort vcam-1 density and tumor perfusion predict t-cell infiltration and treatment response in preclinical models()()
topic Original article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6744528/
https://www.ncbi.nlm.nih.gov/pubmed/31521051
http://dx.doi.org/10.1016/j.neo.2019.08.003
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