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Regulation of Anti-tumor T Cell Migration and Function: Contribution of Real-Time Imaging

  • Pierre-Louis Loyher
  • Christophe Combadière
  • Alexandre BoissonnasEmail author
Chapter
Part of the Resistance to Targeted Anti-Cancer Therapeutics book series (RTACT, volume 9)

Abstract

Mounting a protective immune response is critically dependent on the orchestrated movement of leucocytes throughout the body. Effector T cells represent a major cell type in the antitumor immune response as they can specifically recognize and target transformed cells. Immunotherapies based on enhancing antitumor T cell functions are being actively developed with many clinical trials underway. Yet, the definition of basic migratory patterns of lymphocytes in various physiological and pathophysiological contexts has only been enabled recently with the use of intravital imaging (IVM) at high resolution. This technology allows to directly visualize the key events of the T cell-mediated immune response in situ including activation, trafficking, interactions with stromal and immune cell components, cell killing but also immune mechanisms suppressing the T cell response. With information on the spatiotemporal contexts of these events it is possible to determine the relative contribution of different cell types during an antitumor T cell response and the major hurdles to successful tumor immune rejection. This chapter will focus on different points for which IVM contributed to our understanding of antitumor T cell migration and function during an endogenous response or after T cell targeted immunotherapies.

Keywords

Intravital Imaging Cell migration Cell interactions Cancer immunotherapy Tumor antigens Immunosuppression Tumor microenvironment Immune checkpoint 

Abbreviations

APCs

Antigen presenting cells

CARS

Coherent anti-stokes raman scattering spectroscopy

CTL

Cytotoxic T lymphocyte

CTLA-4

Cytotoxic T-lymphocyte-associated protein 4

DCs

Dendritic cells

DNA

Deoxyribonucleic acid

ECM

Extra-cellular matrix

GFP

Green fluorescent protein

HIF-1

Hypoxia inductible factor-1

HLA

Human leucocyte antigen

ICAM-1

Intercellular adhesion molecule-1

IDO

Indoleamine 2,3-dioxygenase

IFNγ

Interferon gamma

IL-10

Interleukin 10

IVM

Intra-vital microscopy

LSCM

Laser scanning microscopy

MDSCs

Myeloid-derived suppressor cells

MHC

Major histocompatibility complex

NK

Natural killer cell

NKT

Natural killer T cell

OPO

Optical parameter oscillator

OTI

Ova-specific CD8 T cell

PD-1

Programmed cell death 1

PD-L1

Programmed cell death-ligand 1

RAE-1γ

Ribonucleic acid export protein 1 gamma

Rag

Recombination-activating genes

SCID

Severe combined immunodeficiency

SHG

Second harmonic generation

TAAs

Tumor-associated antigens

TAMs

Tumor-associated macrophages

TCR

T cell receptor

TDLNs

Tumor draining lymph nodes

Teff

T effector lymphocyte

Th

T helper

THG

Third harmonic generation

TILs

Tumor infiltrating lymphocytes

TIM-3

T-cell immunoglobulin mucin receptor 3

TME

Tumor microenvironment

TNFα

Tumor necrosis factor alpha

TPLSM

Two-photon laser scanning microscopy

TRAIL

Tumor-necrosis-factor related apoptosis inducing ligand

TuDCs

Tumor dendritic cells

VEGF-A

Vascular endothelial growth factor-A

WT

Wild type

YFP

Yellow fluorescent protein

Notes

Acknowledgments

The writing of this chapter has been possible thanks to the European Community’s Seventh Framework Programme (FP7/2007–2013) under grant agreement no. 304810—RAIDs, la “Ligue contre le cancer”, and “Association pour la Recherche sur le Cancer”.

The authors declare that they have no conflict of interest.

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Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Pierre-Louis Loyher
    • 1
  • Christophe Combadière
    • 1
  • Alexandre Boissonnas
    • 1
    Email author
  1. 1.Sorbonne Universités, UPMC Université Paris 06 UMR_S1135, IUC, Inserm U1135, CNRS ERL8255, Centre d’Immunologie et des Maladies InfectieusesParisFrance

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