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Tregs: Treacherous cells offer a new therapeutic target in colorectal cancer

Scientists have linked a subset of T cells to the progression of colorectal cancer tumours. Researchers also showed that blocking a receptor on these cells with an antibody, suppressed cancer progression. This suggests a similar approach could help treat this deadly malignancy.

Researchers at the Center for Fundamental Immunology in Seattle, USA, investigated the  relationship between regulatory T cells (Tregs ) and tumour-derived cytokine thymic stromal lymphopoietin (TSLP) in colorectal cancer (CRC).

The study, published in Science Translational Medicine, was conducted in mice and samples from human patients.

“TSLP signalling in both effector and Tregs  is important for their homeostasis and function in the skin. However, a role for TSLP in the function of colonic T cells is not well understood,” note the authors.  

TSLP as a biomarker

Regulatory T cells (Tregs) are a well-known marker of cancer progression. TSLP is thought to influence Tregs functions in tumours.

TSLP is an IL-7–like cytokine produced primarily by epithelial cells at barrier surfaces, including in the colon. It has been linked to the progression of several human cancers including breast, pancreatic, gastric, and cervical.

The authors reported, “We found that high expression of TSLP in cancer cells is a risk factor for severity of CRCs in human patients.” 

The researchers found that the expression of TSLP in tumours was not related to the stage of the cancer. This suggested that TSLP was expressed throughout tumour progression. Subsequently, it could be a potential biomarker of poor prognosis of CRC.

Distinct Tregs identified

Obata-Ninomiya et al performed gene expression analysis of the four populations of Tregs in the colons of naïve and tumour-bearing animals, using RNA sequencing (RNA-seq). They revealed distinct subpopulations of Tregs that markedly changed during development of cancer.

The researchers saw Tregs expressing the receptor for TSLP that that were increased in colorectal tumours in humans and mice and largely absent in adjacent normal colon. This Treg subset was also found in the peripheral blood of patients with colon cancer but not in the peripheral blood of healthy control subjects. 

Blocking TSLP to inhibit tumours

Therapeutic blockade of TSLP using TSLP-specific monoclonal antibodies effectively inhibited the progression of colorectal tumours in this mouse model. They treated a chemically induced CRC mouse model with TSLP monoclonal antibodies. This inhibited the progression of colorectal tumours in this mouse model.

While the study has shown that loss of TSLP signalling by Tregs, either genetically or through antibody-mediated blockade, discourages tumour development, it has not identified the operative TSLP-expressing cell type in the colon. This is currently an area of active study.

TSLP represents a potential therapeutic target to regulate Treg function and control CRC progression.

The authors note, “Although these studies are limited to mouse models, the approval of tezepelumab (anti-TSLP) to treat asthma in humans provides the possibility that these studies can be translated to human disease.”

It will also be important to extend these studies to other gut-related diseases, such as Inflammatory Bowel Disease , which are associated with the development of CRC. 

Written by Poppy Jayne Morgan

Image Credit: Canva

More on these topics

Biomarkers / Colorectal / RNA sequencing / T cell