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Chemokine Receptors and Exercise to Tackle the Inadequacy of T Cell Homing to the Tumor Site

While cancer immune therapy has revolutionized the treatment of metastatic disease across a wide range of cancer diagnoses, a major limiting factor remains with regard to relying on adequate homing of anti-tumor effector cells to the tumor site both prior to and after therapy. Adoptive cell transfer...

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Detalles Bibliográficos
Autores principales: Idorn, Manja, thor Straten, Per
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6115859/
https://www.ncbi.nlm.nih.gov/pubmed/30126117
http://dx.doi.org/10.3390/cells7080108
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author Idorn, Manja
thor Straten, Per
author_facet Idorn, Manja
thor Straten, Per
author_sort Idorn, Manja
collection PubMed
description While cancer immune therapy has revolutionized the treatment of metastatic disease across a wide range of cancer diagnoses, a major limiting factor remains with regard to relying on adequate homing of anti-tumor effector cells to the tumor site both prior to and after therapy. Adoptive cell transfer (ACT) of autologous T cells have improved the outlook of patients with metastatic melanoma. Prior to the approval of checkpoint inhibitors, this strategy was the most promising. However, while response rates of up to 50% have been reported, this strategy is still rather crude. Thus, improvements are needed and within reach. A hallmark of the developing tumor is the evasion of immune destruction. Achieved through the recruitment of immune suppressive cell subsets, upregulation of inhibitory receptors and the development of physical and chemical barriers (such as poor vascularization and hypoxia) leaves the microenvironment a hostile destination for anti-tumor T cells. In this paper, we review the emerging strategies of improving the homing of effector T cells (TILs, CARs, TCR engineered T cells, etc.) through genetic engineering with chemokine receptors matching the chemokines of the tumor microenvironment. While this strategy has proven successful in several preclinical models of cancer and the strategy has moved into the first phase I/II clinical trial in humans, most of these studies show a modest (doubling) increase in tumor infiltration of effector cells, which raises the question of whether road blocks must be tackled for efficient homing. We propose a role for physical exercise in modulating the tumor microenvironment and preparing the platform for infiltration of anti-tumor immune cells. In a time of personalized medicine and genetic engineering, this “old tool” may be a way to augment efficacy and the depth of response to immune therapy.
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spelling pubmed-61158592018-08-31 Chemokine Receptors and Exercise to Tackle the Inadequacy of T Cell Homing to the Tumor Site Idorn, Manja thor Straten, Per Cells Review While cancer immune therapy has revolutionized the treatment of metastatic disease across a wide range of cancer diagnoses, a major limiting factor remains with regard to relying on adequate homing of anti-tumor effector cells to the tumor site both prior to and after therapy. Adoptive cell transfer (ACT) of autologous T cells have improved the outlook of patients with metastatic melanoma. Prior to the approval of checkpoint inhibitors, this strategy was the most promising. However, while response rates of up to 50% have been reported, this strategy is still rather crude. Thus, improvements are needed and within reach. A hallmark of the developing tumor is the evasion of immune destruction. Achieved through the recruitment of immune suppressive cell subsets, upregulation of inhibitory receptors and the development of physical and chemical barriers (such as poor vascularization and hypoxia) leaves the microenvironment a hostile destination for anti-tumor T cells. In this paper, we review the emerging strategies of improving the homing of effector T cells (TILs, CARs, TCR engineered T cells, etc.) through genetic engineering with chemokine receptors matching the chemokines of the tumor microenvironment. While this strategy has proven successful in several preclinical models of cancer and the strategy has moved into the first phase I/II clinical trial in humans, most of these studies show a modest (doubling) increase in tumor infiltration of effector cells, which raises the question of whether road blocks must be tackled for efficient homing. We propose a role for physical exercise in modulating the tumor microenvironment and preparing the platform for infiltration of anti-tumor immune cells. In a time of personalized medicine and genetic engineering, this “old tool” may be a way to augment efficacy and the depth of response to immune therapy. MDPI 2018-08-17 /pmc/articles/PMC6115859/ /pubmed/30126117 http://dx.doi.org/10.3390/cells7080108 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Idorn, Manja
thor Straten, Per
Chemokine Receptors and Exercise to Tackle the Inadequacy of T Cell Homing to the Tumor Site
title Chemokine Receptors and Exercise to Tackle the Inadequacy of T Cell Homing to the Tumor Site
title_full Chemokine Receptors and Exercise to Tackle the Inadequacy of T Cell Homing to the Tumor Site
title_fullStr Chemokine Receptors and Exercise to Tackle the Inadequacy of T Cell Homing to the Tumor Site
title_full_unstemmed Chemokine Receptors and Exercise to Tackle the Inadequacy of T Cell Homing to the Tumor Site
title_short Chemokine Receptors and Exercise to Tackle the Inadequacy of T Cell Homing to the Tumor Site
title_sort chemokine receptors and exercise to tackle the inadequacy of t cell homing to the tumor site
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6115859/
https://www.ncbi.nlm.nih.gov/pubmed/30126117
http://dx.doi.org/10.3390/cells7080108
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