September 24, 2021

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Mayo Clinic | University of Chicago: Which gene can control colon cancer?

Mayo Clinic | University of Chicago: Which gene can control colon cancer?

Mayo Clinic | University of Chicago: Which gene can control colon cancer?



Mayo Clinic | University of Chicago: Which gene can control colon cancer? Scientists from Mayo Clinic and University of Chicago will tell you the answer!

Introduction:

Colon cancer refers to malignant tumors that occur in the colon. According to the location of occurrence, it is divided into ascending colon cancer, transverse colon cancer, descending colon cancer, sigmoid colon cancer, and rectal cancer. Among them, ascending colon cancer and transverse colon cancer are also called right colon cancer.

Descending colon cancer and sigmoid colon cancer, also known as left colon cancer, and rectal cancer. The treatment of colon cancer is based on surgery and postoperative chemotherapy. The treatment of rectal cancer often involves radiotherapy and chemotherapy before surgery, followed by surgical resection, and adjuvant chemotherapy after surgery according to the situation.

For metastatic bowel cancer, systemic therapy is still the mainstay, including chemotherapy and targeted therapy. Recently, scientists have carried out in-depth exploration of colon cancer and made new discoveries…

Regulatory cell (Regulatory cell, Treg for short) is a type of T cell subgroup that controls autoimmune reactivity in the body.

Regulatory T cells can be divided into naturally occurring natural regulatory T cells (nTreg) and induced adaptive regulatory T cells (aTreg or iTreg), such as Th3, Tr1, CD8 Treg, NKT cells, etc., and their own The occurrence of immune diseases is closely related, and its abnormal expression can lead to autoimmune diseases. Among them, Tr1 cells secrete IL-10; Th3 cells secrete TGF-β; in 1995, Sakaguchi found that nearly 10% of peripheral CD4+ T cells in adult mice express IL-2 receptor α chain CD25.

Removal of this group of cells will cause the mice to spontaneously develop a variety of autoimmune diseases, and the infusion of the cells will prevent the occurrence of diseases. Therefore, this group of cells was named CD4+CD25+ regulatory T cells Treg.

Regulatory T cells are also related to the onset of many autoimmune diseases such as rheumatoid arthritis, autoimmune thyroiditis, autoimmune liver disease, and various kidney diseases.

Regulatory T cells are of great significance to the occurrence and development of autoimmune diseases. In-depth research on them will help to understand the pathogenesis of autoimmune diseases, and have far-reaching significance for disease prognosis judgment and further treatment.

Scientists from Purdue University, Mayo Clinic, and the University of Chicago have studied the regulation of Treg cells. This team of scientists published their research results in an article titled “TCF-1 controls Treg cell functions that regulate inflammation, CD8+ T cell cytotoxicity and severity of colon cancer” in the journal Nature Immunology:

Mayo Clinic | University of Chicago: Which gene can control colon cancer?

The transcription factor TCF-1 is essential for the development and function of regulatory T (Treg) cells; however, little is known about its function. Through the research of scientists: They found that TCF-1 mainly inhibits the transcription of genes that Foxp3 binds together.

Single-cell RNA sequencing analysis revealed that effector memory T cells and central memory Treg cells differentially expressed Klf2 and memory and activation markers. TCF-1 deficiency does not change the transcriptional characteristics of core Treg cells, but promotes alternative signaling pathways, so that Treg cells are activated, and the intestinal homing characteristics and characteristics of the TH17 subset of helper T cells are obtained.

TCF-1 deficient Treg cells strongly inhibit T cell proliferation and cytotoxicity, but are inhibited in controlling CD4+ T cell polarization and inflammation. In polyposis mice, Treg cell-specific TCF-1 deficiency promotes tumor growth.

Compared with adjacent normal tissues and circulating T cells, tumor-infiltrating Treg cells in colorectal cancer patients have lower TCF-1 expression levels and higher TH17 expression characteristics.

Therefore, Treg cell-specific TCF-1 expression differentially regulates TH17-mediated inflammation and T cell cytotoxicity, and can determine the prognosis of colorectal cancer.

Regulatory T cells (Treg) are essential for regulating the immune system. However, there are several different types of Treg cells, and scientists are only just beginning to distinguish between them and explore their functions and roles.

Researchers from Purdue University, including Majid Kazemian, assistant professor of biochemistry and computer science, and a group of collaborators from the Mayo Clinic and the University of Chicago, discovered that the TCF-1 gene controls a specific set of Treg cells Function.

Without TCF-1, these Treg cells will maintain their normal inhibitory function, but they can acquire additional properties and easily cause inflammation and become more active. At this time, cancer signals will increase and intestinal homing will be achieved. Characteristics that ultimately lead to more severe and riskier colon cancer. Colon cancer patients also have the same Treg cells lacking TCF-1 in their tumors.

Before this study, scientists knew many major regulatory factors, but this is the first time that the link between TCF-1 and colon cancer has been explored. Future drug development will focus on this approach to treat or improve certain types of colon cancer.

Scientists began to study the connection between TCF-1 and Treg cells. They found that when TCF-1 was removed, Treg cells changed their behavior and became intestinal cells, which are more abundant. They studied the activity of Treg cells in mice lacking the gene and compared it with the activity of Treg cells in colon cancer patients.

Kazemian explained: “It is extremely important to be able to control the degree of immune response, which is why it is particularly important to understand these Treg cells. If the Treg cells respond too much, they will produce autoimmunity; but if there is too little, you will get cancer. .

The healthy system needs to strike a balance between autoimmune diseases and cancer, and proper Treg cell function plays a very critical role in this regard. “

(source:internet, reference only)


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