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Disruption of Anti-tumor T Cell Responses by Cancer-Associated Fibroblasts

  • Arnaud PommierEmail author
  • Douglas T. Fearon
Chapter
Part of the Resistance to Targeted Anti-Cancer Therapeutics book series (RTACT, volume 9)

Abstract

Tumors arise from the malignant transformation of normal cells through genetic dysregulation of the cell growth controls. However, cancer cells are not the only component of a tumor and the non-cancer cell part of the tumor has been termed stroma. The tumor stroma comprises cells of at least three different origins: endothelial, mesenchymal and hematopoietic, thereby forming a complex microenvironment. Among these three elements, immune cells have been extensively studied for the last 20 years because of their potential tumoricidal properties. However, immunologists failed to efficiently harness the immune system’s anti-tumor properties until very recently, shedding light on a very complex immuno-suppressive network in tumor-bearing hosts. The mesenchymal part of the tumor, the so-called cancer-associated fibroblasts (CAFs), is among those actors of the tumor that have been disregarded despite their crucial role. Indeed, CAFs have been recently shown to be one of the more potent immune-suppressive cells of the tumor micro-environment. This chapter focuses on their roles on immune components of the tumor micro-environment, especially T cells. CAFs can impact T cells in two major ways: Disruption of T cell homeostasis and functions, and exclusion of T cells from the vicinity of tumor cells. These recent advances in the understanding the tumor micro-environment reveals potential new ways for attacking tumor cells.

Keywords

Anti-tumor immune response T cells Cancer-associated fibroblasts Immunotherapies 

Abbreviations

Ab

Antibody

APCs

Antigen presenting cells

CAFs

Cancer-associated fibroblasts

CSC

Cancer stem cell

CTL

Cytotoxic T cells

CTLA-4

Cytotoxic T lymphocyte antigen-4

DCs

Dendritic cells

ECM

Extracellular matrix

EMT

Epithelial-to-mesenchymal transition

FAP

Fibroblast activation protein

FRCs

Fibroblastic reticular cells

FSP1

Fibroblast specific protein-1

HCC

Hepatocellular carcinoma

HGF

Hepatocyte growth factor

HO-1

Heme oxidase-1

HSCs

Hepatic stellate cells

IDO

Indolamine-2,3-dioxygenase

IFN

Interferon

IL

Interleukin

ITIM

Immunoreceptor tyrosine inhibitory motif

LOX

Lysyl-oxidase

MDSCs

Myeloid derived suppressor cells

MHC

Major hiscompatibility complex

MLR

Mixed lymphocyte reaction

MMPs

Matrix metalloproteases

MSCs

Mesenchymal stem cells

NSCLC

Non-small cell lung carcinoma

PD-1

Programmed death-1

PD-L1

Programmed death ligand-1

PDAC

Pancreatic ductal adenocarcinoma

PDGF

Platelet-derived growth factor

PGE2

Prostaglandin E2

PSCs

Pancreatic stellate cells

ROS

Reactive oxygen species

α-SMA

α-Smooth muscle actin

TAMs

Tumor-associated macrophages

TGFβ

Transforming growth factor β

TLSs

Tertiary lymphoid structures

Tregs

Regulatory T cells

TSLP

Thymic stromal lymphopoietin

Notes

Acknowledgements

The authors would like to thank Mickael Ludwig, Jia-Yun Li and Zhikai Wang for critical reading.

No potential conflicts of interest were disclosed.

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Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Cold Spring Harbor LaboratoryCold Spring HarborUSA
  2. 2.Weill Cornell Medical CollegeNew YorkUSA

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