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

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Defects in T Cell Trafficking and Resistance to Cancer Immunotherapy

Part of the book series: Resistance to Targeted Anti-Cancer Therapeutics ((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.

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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

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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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Authors and Affiliations

  1. Adaptive Immunity Laboratory, Humanitas Clinical and Research Center, Via Manzoni 56, Rozzano (Milano), Italy

    Stefano Garetto, Claudia Sardi & Marinos Kallikourdis

  2. Humanitas Clinical and Research Center, Via Manzoni 56, Rozzano (Milano), Italy

    Diego Morone

  3. Humanitas University, Via Manzoni 113, Rozzano (Milano), Italy

    Marinos Kallikourdis

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  1. Stefano Garetto
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  2. Claudia Sardi
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Correspondence to Marinos Kallikourdis .

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

    Emmanuel Donnadieu

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Garetto, S., Sardi, C., Morone, D., Kallikourdis, M. (2016). Chemokines and T Cell Trafficking into Tumors: Strategies to Enhance Recruitment of T Cells into Tumors. 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_7

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