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New discoveries may pave the way for more effective cancer immunotherapy

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A type of white blood cell, formerly known only as a helper to the immune system, also appears to be an instigator of the body’s defense against cancerous tumors. This finding may lead to more effective cancer immunotherapy. This is a promising treatment that uses the body’s own immune system, rather than radiation, to attack cancer cells.

In animal experiments, researchers at Washington State University T cells What are called CD4-positive helper T cells helped initiate a series of anti-tumor immune defenses that allow killer cells to infiltrate better. melanoma And breast cancer tumors. T cells belong to a class of white blood cells called lymphocytes that travel throughout the body’s lymphatic system.

Many previous studies and current immunotherapies have primarily focused on the role of one type of killer cell called a CD8-positive T cell. Still, less than 20% of patients respond to these therapies, and the role of initiation of CD4-positive helper cells may improve these therapies, Immunology Journal.

One of the most difficult parts of cancer immunotherapy today is low response rates. Lack of knowledge about how to enhance lymphocyte infiltration into tumors impedes success in improving response to cancer immunotherapy. Our findings show promise in solving this problem. “


Hui Chang, Associate Professor of WSU in Pharmaceutical Sciences

Cancer is the second leading cause of death in Japan and around the world. Today, surgery, chemotherapy, and radiation therapy are traditional approaches to cancer treatment. However, these approaches do not cure many cancers. This is because some cancers become metastatic, spread systemically from the primary tumor, and certain cancer stem cells may become resistant to chemotherapy and radiation therapy.

Immunotherapy, a relatively new treatment, has shown promise in treating a variety of cancers, but relatively few patients respond to it. Zhang’s research team wants to change that with knowledge of the mechanisms that help the body initiate immune defense.

There are two types of killer cells in the immune system: CD8-positive T cells and so-called “natural killer” cells. Both can attack virus-infected cells and cancer cells.

Natural killer cells are innate and roam around the body. They serve as a front-line defense of our immune system, but they cannot recognize specific antigens (toxins or other foreign substances in the body) alone. After the natural killer cells start working, CD8-positive T cells that can recognize specific antigens arrive. Although CD8-positive T cells and their mechanisms are well-studied and used in current immunotherapy, little is known about how to activate the antitumor function of natural killer cells.

Using gene knockout mouse experiments, Zhang’s group found that certain types of CD4-positive T cells, called memory T cells, present in tissues are important for activating the first lineage of natural killer cell defense factors. I have found evidence that it may be. Their experiments have shown that they are effective against both melanoma and breast cancer tumors.

“We have found that this particular population of CD4 T cells is an important player in initiating antitumor immunity,” Zhang said.

Certain CD4T cells, along with natural killer cells, killed tumor cells and not only controlled tumor progression, but also promoted infiltration of other white blood cells or lymphocytes into the tumor.

In future studies, researchers plan to continue investigating the exact cellular and molecular mechanisms of this antitumor immunity-first developing effective cancer immunotherapy in mice. After that, the team wants to proceed to clinical trials in humans.

“Our goal is to develop a powerful cancer immunotherapy approach that is effective for all patients with different types of cancer,” says Zhang.

This study was supported by startup funding from the National Institutes of Health and the WSU Pharmacy and Faculty of Pharmacy.

sauce:

Journal reference:

Zhang, H., et al. (2022) Memory CD4 + T cells present in tissues play a dominant role in initiating antitumor immunity. Immunology Journal. doi.org/10.4049/jimmunol.2100852..

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