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

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Book cover Defects in T Cell Trafficking and Resistance to Cancer Immunotherapy

Part of the book series: Resistance to Targeted Anti-Cancer Therapeutics ((RTACT,volume 9))

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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.

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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

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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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Authors and Affiliations

  1. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA

    Arnaud Pommier & Douglas T. Fearon

  2. Weill Cornell Medical College, New York, NY, USA

    Arnaud Pommier & Douglas T. Fearon

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  1. Arnaud Pommier
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  2. Douglas T. Fearon
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Correspondence to Arnaud Pommier .

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

    Emmanuel Donnadieu

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Pommier, A., Fearon, D.T. (2016). Disruption of Anti-tumor T Cell Responses by Cancer-Associated Fibroblasts. 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_4

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