Homing Improvement: Boosting T Cell Trafficking for Cancer Immunotherapy

  • Joseph M. CantorEmail author
Part of the Resistance to Targeted Anti-Cancer Therapeutics book series (RTACT, volume 9)


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.


T cell Immunotherapy Homing Trafficking Integrin Chemokine Migration 



Adoptive cellular tumor immunotherapy


Acute myeloid leukemia


Chimeric antigen receptor


Chemokine receptor 9


Chronic myeloid leukemia


Clustered regularly-interspaced short palindromic repeats


Cytotoxic T lymphocyte-associated protein 4


Dendritic cell


Epidermal growth factor receptor


Focal adhesion kinase


Intercellular adhesion molecule 1


Interleukin 1 beta


Interleukin 2


Interleukin 6


Intravenous immunoglobulin


Leukocyte functional adhesion molecule 1


Natural killer cell


Programmed cell death protein 1


Protein kinase A, Type I


Stem cell-derived factor 1 alpha


Tumor-associated antigen(s)


Central memory T cell


T cell receptor


Effector memory T cell


Tumor-infiltrating lymphocyte(s)


Tumor lysis syndrome


Tumor necrosis factor-alpha


Tumor-specific antigen(s)


Vascular cell adhesion molecule 1


Vascular endothelial growth factor receptor


Very late activation antigen 4



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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© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Department of MedicineUniversity of California San DiegoLa JollaUSA

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