The researchers identified a type of T cell known as CD4-positive helper T cells. These T cells contributed to the development of a series of antitumor immune mechanisms that allow killer cells to infiltrate more deeply into melanoma and breast cancer tumors.
The finding could improve cancer immunotherapy, a promising therapy that targets cancer cells using the body’s own immune system instead of radiation.
Once thought of as just a helper for the immune system, a type of white blood cell now appears to be the initiator of the body’s defenses against cancerous tumors. The finding could improve cancer immunotherapy, a promising treatment that targets cancer cells using the body’s own immune system instead of radiation.
Washington State University researchers discovered in an animal study that a population of T cells known as CD4-positive helper T cells contributed to the initiation of a chain of antitumor immunity defenses that enhance the ability of killer cells to infiltrate melanoma and breast cancer tumors. T cells are a subset of white blood cells called lymphocytes, which circulate throughout the body via the lymphatic system.
The involvement of a specific subset of killer cells known as CD8-positive T cells has been the focus of several previous studies as well as contemporary immunotherapies. However, less than 20% of patients respond to these treatments, and Hui Zhang, the study’s lead author, suggested that the early role of CD4-positive helper cells could improve these treatments. The findings were recently published in the Journal of Immunology.
“One of the most challenging parts of current cancer immunotherapy is the low response rate,” said Zhang, assistant professor of pharmaceutical sciences at WSU. “The lack of knowledge of how to improve lymphocyte infiltration into the tumor hinders the success of improving the response rate to cancer immunotherapy. Our finding holds promise for solving this problem.”
Cancer is the second leading cause of death both nationally and worldwide. Currently, surgery, chemotherapy, and radiation therapy are the conventional approaches to cancer treatment. However, these approaches cannot cure many cancers because some become metastatic, spreading from the primary tumor throughout the body, and some cancer stem cells can become resistant to chemotherapy and radiation.
A relatively new treatment, immunotherapy has shown promise in curing a number of cancers, but only a relatively small number of patients respond to it. Zhang’s research team hopes to change that with knowledge of the mechanisms that help initiate the body’s immune defenses.
The immune system has two types of killer cells: 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 the body. They act as our immune system’s first line of defense, but they cannot recognize specific antigens (toxins or other foreign substances in the body) on their own. After natural killer cells start working, CD8-positive T cells arrive, which can recognize specific antigens. Although CD8-positive T cells and their mechanisms have been well studied and used in current immunotherapies, not much is known about how to activate the antitumor function of natural killer cells.
Using genetic mouse experiments, Zhang’s group found evidence that a certain type of CD4-positive T cells, called tissue-resident memory T cells, may be critical for activating these first lines of cell defenders natural killers Their experiments showed that they were effective against both melanoma and breast cancer tumors.
“We found that this specific population of CD4 T cells was the key player in initiating antitumor immunity,” Zhang said.
Specific CD4 T cells together with natural killer cells not only killed tumor cells and controlled tumor progression, but also enhanced the infiltration of other white blood cells, or lymphocytes, into the tumor .
In future studies, the researchers plan to continue investigating the precise cellular and molecular mechanisms of this antitumor immunity, first in mice to develop effective cancer immunotherapy. The team then hopes to move on to clinical trials in human subjects.
“Our goal is to develop a powerful cancer immunotherapy approach that is effective for all patients with different types of cancer,” Zhang said.
Reference: “Tissue-Resident Memory CD4+ T Cells Play a Dominant Role in Initiation of Antitumor Immunity” by Hui Zhang, Zhaohui Zhu, Samantha Modrak, and Alex Little, June 15, 2022, The Journal of Immunology .DOI: 10.4049/jimmunol.2100852
This study was funded by the National Institutes of Health, as well as seed funds from the WSU College of Pharmacy and Pharmaceutical Sciences.