June 14, 2024

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Lack of this key immune cell may lead to occurrence of colorectal cancer

Lack of this key immune cell may lead to the occurrence of colorectal cancer

Lack of this key immune cell may lead to the occurrence of colorectal cancer. The lack of this key immune cell can affect the intestinal microbes and may lead to the occurrence of colorectal cancer. 

Introduction: Colorectal cancer, its incidence and fatality rate is second only to gastric cancer, esophageal cancer and primary liver cancer. Recently, research published in “Cell” shows that a key immune cell-ILC3s helps to regulate the relationship between the immune system and intestinal microbes to prevent colorectal cancer.

Innate lymphocytes (ILC), also known as innate immune cells, are a subset of lymphocytes that are different from T cells and B cells. They are located on the surface of the intestinal mucosa to enhance immune response, maintain mucosal integrity and promote lymphoid organs form. Studies have shown that ILC3s can infiltrate tumors and affect the occurrence and development of cancer through the production of cytokines.

According to a new study led by researchers at Weill Cornell Medical College and New York Presbyterian Hospital, a subset of immune cells called innate lymphocytes (ILC3s) can protect the human body from colorectal cancer, partly The reason is that it helps maintain a healthy dialogue between the immune system and gut microbes. This discovery opens the door to new strategies to treat this type of cancer.

The researchers published their results in the “Cell” magazine and published an article entitled “Dysregulation of ILC3s unleashes progression and immunotherapy resistance in colon cancer”. The results show that patients with colorectal cancer tend to significantly reduce ILC3s and undergo functional changes. In addition, they also proved that destroying the function of ILC3s in mice through experiments can lead to aggressive colorectal cancer and greatly reduce the effectiveness of cancer immunotherapy. Therefore, the dysregulation of ILC3s will promote the progression of this cancer and resistance to immunotherapy.

Lack of this key immune cell may lead to the occurrence of colorectal cancer

Colorectal cancer is the fourth most common cancer in the United States, with approximately 150,000 new cases and approximately 50,000 deaths each year. Although colonoscopy screening for early detection of these cancers or precancerous polyps is very effective, the treatment of advanced colon tumors is still a major challenge due to limited treatment options. Oncologists pay special attention to the relative resistance of these tumors to immunotherapy, which is effective against other cancers by enhancing the immune system’s ability to attack malignant cells.

Lack of this key immune cell may lead to the occurrence of colorectal cancer

Senior author Dr. Gregory Sonnenberg, associate professor of medical microbiology and immunology in the Department of Gastroenterology and Hepatology, member of the Jill Roberts Institute of Inflammatory Bowel Disease at Weill Cornell College of Medicine, and senior author said: “These findings are a clinical treatment for colorectal cancer. It provides new possibilities and helps explain why this type of cancer is usually ineffective for immunotherapy.”

One factor that affects the resistance of immunotherapy may be the gut microbiome, intestinal bacteria and other microbial populations, which usually help digestion, support various metabolic functions, and play a role in regulating the immune system. Colorectal cancer is associated with chronic intestinal inflammation and severe destruction of the normal microbiota. In addition, recent studies have shown that the patient’s microbiome plays a key role in controlling the outcome of cancer immunotherapy, and may explain why some patients’ cancers respond well or not to treatment.

In this new study, Dr. Sonnenberg and his colleagues, including Dr. Jeremy Goc, a research assistant in Dr. Sonnenberg’s laboratory and senior author, jointly studied the role of ILC3s. ILC3s are found in the intestine and are thought to help regulate the relationship between the immune system and the intestinal microbes.

ILC3s usually play a key role in maintaining a healthy dialogue between the lower gut microbiome and the immune environment. In close collaboration with Dr. Manish Shah, Professor of Gastrointestinal Oncology in the Bartlett Family, Director of the Gastrointestinal Oncology Program of the Division of Hematology and Medical Oncology, and member of Sandra and Edward Meyer Cancer Center of Weill Cornell Medical College, the research team analyzed human and Colorectal cancer and precancerous polyps in mice. They found that compared with healthy tissues, ILC3s in cancer tissues were relatively reduced, and its function was further fundamentally changed.

Dr. Shah, director of the Solid Tumor Oncology Service, co-director of the New York Presbyterian and Weill Cornell Medical Center’s Advanced Digestive Care Center, and co-author of the study, said: “This is an exciting discovery for our understanding of controlling the gastrointestinal tract The pathogenesis, progression, and treatment response of malignant tumors are of broad significance.”

In the loss of normal ILC3 activity in the intestine, the authors further observed that the ability of ILC3s to regulate a specific subset of immune cells called T cells was severely disrupted. The interruption of the dialogue between ILC3s and T cells further leads to an increase in intestinal inflammation, thereby changing the intestinal microbiome. These changes in intestinal microbes will in turn lead to a decline in the level of T cells, and T cells perform well in fighting tumors.

Researchers show that these common results have a major impact on tumor development. In mice with colorectal cancer, blocking ILC3 signaling resulted in abnormally aggressive and more aggressive tumor growth with a poor prognosis. When colon tumors were implanted in mice whose ILC3 signal was blocked, the tumors were relatively unresponsive to a cancer immunotherapy called anti-PD-1 checkpoint blockade, while the same type of tumor was implanted with small ILC3 signals. After the rats were in vivo, they responded well to the therapy.

Finally, in biopsies of colon tissue from patients with inflammatory bowel disease (IBD), the researchers found that ILC3-related abnormalities were similar to those in patients with colorectal cancer. Transplanting microorganisms from patients with IBD into mice makes the mice resistant to treatment; while transplanting microorganisms from healthy human donors into mice has a good response against PD-1 checkpoint blockade.

Lack of this key immune cell may lead to the occurrence of colorectal cancer

In general, the above studies have defined the protective role of ILC3s in cancer. Dr. Goc said: “A better understanding of the contribution of the microbiome to cancer development and treatment responsiveness can revolutionize patient management strategies. This study sheds light on a resistance mechanism driven by microbiome disorders that has been so far It has not been taken seriously. For example, it shows that one day we can sample the gut microbiota to predict tumor progression and responsiveness to immunotherapy, and even use a healthy microbiota to improve treatment responsiveness.”

Researchers are currently working to determine the types of gut bacteria that are most beneficial in this regard.

(source:internet, reference only)

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