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Defects in T Cell Trafficking and Resistance to Cancer Immunotherapy pp 127–161Cite as

Homing Improvement: Boosting T Cell Trafficking for Cancer Immunotherapy

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Part of the book series: Resistance to Targeted Anti-Cancer Therapeutics ((RTACT,volume 9))

Abstract

Advances in T cell tumor immunotherapy have raised hopes for this approach to become a significant treatment for a variety of cancers. Recent successes in leukemia using CAR-modified T cells and in metastatic melanoma using tumor-infiltrating lymphocytes have provided impetus to expand adoptive cellular immunotherapy into treatment of solid tumors. In this setting, adoptively-transferred T cells face a hostile tumor environment that suppresses their anti-tumor functions. In addition, T cells activated and expanded outside of the lymph node lack naturally imprinted homing cues and often exhibit poor homing to most sites of tumor growth. This significant problem has limited the application of cellular tumor immunotherapy to a select few malignancies. However, new ideas to improve the migration of transferred T cells have been generated and tested in preclinical models. Super-charging inflammatory migration of T cells is possible by modulating any number of components in the leukocyte migration machinery, from chemo-attractants, to integrins, to extracellular matrix adhesion ligands. Promising results suggest that the homing problem can indeed be overcome to remove a major barrier in allowing cellular tumor immunotherapy to achieve its full potential as a cancer treatment.

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Abbreviations

ACT:

Adoptive cellular tumor immunotherapy

AML:

Acute myeloid leukemia

CAR:

Chimeric antigen receptor

CCR9:

Chemokine receptor 9

CML:

Chronic myeloid leukemia

CRISPR:

Clustered regularly-interspaced short palindromic repeats

CTLA-4:

Cytotoxic T lymphocyte-associated protein 4

DC:

Dendritic cell

EGFR:

Epidermal growth factor receptor

FAK:

Focal adhesion kinase

ICAM-1:

Intercellular adhesion molecule 1

IL-1β:

Interleukin 1 beta

IL-2:

Interleukin 2

IL-6:

Interleukin 6

IVIG:

Intravenous immunoglobulin

LFA-1:

Leukocyte functional adhesion molecule 1

NK:

Natural killer cell

PD-1:

Programmed cell death protein 1

PKA-I:

Protein kinase A, Type I

SDF-1α:

Stem cell-derived factor 1 alpha

TAA:

Tumor-associated antigen(s)

TCM :

Central memory T cell

TCR:

T cell receptor

TEM :

Effector memory T cell

TIL(s):

Tumor-infiltrating lymphocyte(s)

TLS:

Tumor lysis syndrome

TNF-α:

Tumor necrosis factor-alpha

TSA:

Tumor-specific antigen(s)

VCAM-1:

Vascular cell adhesion molecule 1

VEGFR:

Vascular endothelial growth factor receptor

VLA-4:

Very late activation antigen 4

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Acknowledgements

The author would like to thank Dr. Mark H. Ginsberg and Dr. David M. Rose for their contributions to the integrin transregulation studies.

No potential conflicts of interest were disclosed.

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  1. Department of Medicine, University of California San Diego, MC 0726, 9500 Gilman Drive, La Jolla, CA, 92093-0726, USA

    Joseph M. Cantor

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  1. Institut Cochin INSERM, Université Paris Descartes, Paris, France

    Emmanuel Donnadieu

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Cantor, J.M. (2016). Homing Improvement: Boosting T Cell Trafficking for Cancer Immunotherapy. In: Donnadieu, E. (eds) Defects in T Cell Trafficking and Resistance to Cancer Immunotherapy. Resistance to Targeted Anti-Cancer Therapeutics, vol 9. Springer, Cham. https://doi.org/10.1007/978-3-319-42223-7_6

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