Regulatory T cells in gastrointestinal tumors

Abstract

Regulatory T cells (Tregs) have the ability to suppress the activity of most other lymphoid cells, as well as dendritic cells through cell–cell contact-dependent mechanisms, which have not yet been fully defined. Tregs are a key component of a functional immune system and Treg deficiency is associated with severe autoimmunity and allergies. However, Tregs specific for tumor-associated antigens are present in cancer patients and Tregs accumulate in many types of solid tumors, where they probably act to promote tumor escape from cytotoxic immune responses. Indeed, some studies even show a negative correlation between Treg infiltration and survival of the patient. Several studies indicate an active recruitment of Tregs to the tumor site and the mechanisms of Treg accumulation are starting to be better understood as a result of more detailed analysis of their adhesion molecule and chemokine receptor expression. In addition, in gastrointestinal tumors there is an increase in tumor-associated Tregs, but intriguingly, Treg infiltration into colorectal adenocarcinomas is associated with improved prognosis. In this article, we will review the proposed mechanisms of immune suppression by tumor-associated Tregs, how the tumor microenvironment favors immune evasion and Treg induction, the tumor-homing mechanisms of Tregs and how Tregs affect progression of gastric and colorectal tumors.

Keywords::

• chemokines
• FoxP3
• gastrointestinal tumors
• immune suppression
• immunotherapy
• regulatory T cells
• TGF-β
• Tregs

Financial & competing interests disclosure

The cited work by Marianne Quiding-Järbrink was supported by The Swedish Research Council, the Swedish Cancer Foundation and grants for clinical research (LUA/Alf) from Sahlgrenska University Hospital. Sukanya Raghavan is supported by the MIVAC Swedish Foundation for Strategic Research Centre (The Centre for Mucosal Immunobiology and Vaccines). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.