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Chemokines and T Cell Trafficking into Tumors: Strategies to Enhance Recruitment of T Cells into Tumors

  • Stefano Garetto
  • Claudia Sardi
  • Diego Morone
  • Marinos KallikourdisEmail author
Chapter
Part of the Resistance to Targeted Anti-Cancer Therapeutics book series (RTACT, volume 9)

Abstract

Chemokines are small proteins used by the cells of the immune system in order to orchestrate their movement in the body during physiological and pathological conditions. Yet they are also expressed in tumors and their metastases. There, they mediate a variety of tumor-specific functions, including the recruitment of different immune cell populations to the tumor site. These cells may have a pro- or anti-tumoral function. Yet the cells mediating the latter are often prevented from infiltrating the tumor mass, due to functional or physical barriers. This is a major obstacle for successful tumor immunotherapy based on cytotoxic T cell administration. Genetic and other pre-clinical studies have provided insights into the mechanisms that regulate these barriers, such as the peri-tumoral fibrotic capsule. Recent novel strategies involving modification of the chemokine receptors expressed in the transferred cytotoxic T cells are providing a possible means of overcoming such obstacles. Integration of such strategies in immunotherapy protocols may hopefully pave the way to a more successful clinical application of T cell immunotherapy.

Keywords

Tumor T cells Adoptive Cell Therapy Recruitment Chemokines Chemokine receptors 

Abbreviations

ACT

Adoptive cell therapy

CAF

Cancer-associated fibroblasts

CAR

Chimeric antigen receptor

ECM

Extra cellular matrix

FAP

Fibroblast Activation Protein-α

GPCR

G-protein-coupled receptors

MDSC

Myeloid-derived suppressor cells

NK

Natural Killer

SHG

Second harmonic generation

TAM

Tumor-associated macrophages

TCR

T cell antigen receptor

TIL

Tumor infiltrating Lymphocytes

Treg

Regulatory T cells

VEGF

Vascular endothelial growth factor

Notes

Acknowledgments

This work was supported by AIRC (MFAG10752), the Italian Ministry of Health (GR-2009-1558698) and FIRB RBFR10HP97. We would like to thank Dr R Bonecchi for helpful comments.

Conflict of interest statement:

 The authors declare that they have no potential conflicts of interest.

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Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Stefano Garetto
    • 1
  • Claudia Sardi
    • 1
  • Diego Morone
    • 2
  • Marinos Kallikourdis
    • 1
    • 3
    Email author
  1. 1.Adaptive Immunity Laboratory, Humanitas Clinical and Research CenterRozzano (Milano)Italy
  2. 2.Humanitas Clinical and Research CenterRozzano (Milano)Italy
  3. 3.Humanitas UniversityRozzano (Milano)Italy

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