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

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


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.


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





Antigen presenting cells


Cancer-associated fibroblasts


Cancer stem cell


Cytotoxic T cells


Cytotoxic T lymphocyte antigen-4


Dendritic cells


Extracellular matrix


Epithelial-to-mesenchymal transition


Fibroblast activation protein


Fibroblastic reticular cells


Fibroblast specific protein-1


Hepatocellular carcinoma


Hepatocyte growth factor


Heme oxidase-1


Hepatic stellate cells








Immunoreceptor tyrosine inhibitory motif




Myeloid derived suppressor cells


Major hiscompatibility complex


Mixed lymphocyte reaction


Matrix metalloproteases


Mesenchymal stem cells


Non-small cell lung carcinoma


Programmed death-1


Programmed death ligand-1


Pancreatic ductal adenocarcinoma


Platelet-derived growth factor


Prostaglandin E2


Pancreatic stellate cells


Reactive oxygen species


α-Smooth muscle actin


Tumor-associated macrophages


Transforming growth factor β


Tertiary lymphoid structures


Regulatory T cells


Thymic stromal lymphopoietin



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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