Next Article in Journal
The Channel-Kinase TRPM7 as Novel Regulator of Immune System Homeostasis
Previous Article in Journal
Targeting the Multidrug Transporter Ptch1 Potentiates Chemotherapy Efficiency
Article Menu
Issue 8 (August) cover image

Export Article

Open AccessReview
Cells 2018, 7(8), 108; https://doi.org/10.3390/cells7080108

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

1
Center for Cancer Immune Therapy, Herlev Gentofte University Hospital, Herlev Ringvej 75, 2730 Herlev, Denmark
2
Department of Immunology and Microbiology, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark
*
Author to whom correspondence should be addressed.
Received: 27 June 2018 / Revised: 9 August 2018 / Accepted: 13 August 2018 / Published: 17 August 2018
(This article belongs to the Special Issue Emerging Cellular Therapies: T Cells and Beyond)
Full-Text   |   PDF [1269 KB, uploaded 17 August 2018]   |  

Abstract

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. View Full-Text
Keywords: adoptive cell therapy; ACT; tumor infiltrating lymphocytes; TIL; genetic engineering; CARs; exercise; chemokines; homing adoptive cell therapy; ACT; tumor infiltrating lymphocytes; TIL; genetic engineering; CARs; exercise; chemokines; homing
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
SciFeed

Share & Cite This Article

MDPI and ACS Style

Idorn, M.; thor Straten, P. Chemokine Receptors and Exercise to Tackle the Inadequacy of T Cell Homing to the Tumor Site. Cells 2018, 7, 108.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Cells EISSN 2073-4409 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top