The ecosystem surrounding a tumor, also known as the tumor microenvironment, includes immune cells, tissues, blood vessels, and other cells that interact with each other and with tumor cells. Over time, tumors shape this ecosystem in their own interests, monopolizing all nutrients and protecting them from the host's immune attack. In order to better understand the role of the ecosystem in cancer risk, occurrence, and treatment.
Recently, in a research report titled "IL3-Driven T Cell-Basophil Crosstalk Enhances Antitumor Immunity" published in the international journal Cancer Immunology Research, scientists from the Jackson Laboratory and other institutions in the United States not only identified how two immune cells work together to resist cancer, but also revealed the molecular cascade that helps coordinate this attack.
Researcher Chih-Hao "Lucas" Chang said that they focused on cytotoxic T cells, which are a type of immune cell with multiple functions, including the ability to destroy virus-infected cells, resist bacterial infections and other pathogens, and attack tumor cells. Their immune system can eliminate most cancerous cells from the body before they cause problems, but once a tumor is formed, cytotoxic T cells become "exhausted" in the hostile tumor microenvironment and cannot effectively attack the tumor. To this end, researchers are currently investigating why these immune cells are in a "exhausted" state and are beginning to look for potential ways to send signals to immune cells to target tumor tissue.
Figure 1. Enhanced T cell-basophil crosstalk by IL-3 supplementation improves anti-tumor immunity. (Wei J, et al., 2024)
T cells are excellent at recognizing and attacking cancerous cells, but they can become "exhausted" in the tumor microenvironment. They can become overworked and overstimulated, and they can also be starved of glucose and other nutrients by the presence of tumor cells. Helping these cells better maintain their function may improve cancer treatment strategies, especially immunotherapy. Previous research has shown that when cytotoxic T cells are activated, they release signaling molecules called cytokines (interleukin-3, IL-3). It was found that as tumors grow, cytotoxic T cells gradually lose the ability to produce IL-3 in the tumor microenvironment. Subsequently, when the researchers increased the levels of IL-3 in mice with lymphoma or melanoma, they observed a strong anti-tumor effect.
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After further investigation, the researchers found that IL-3 may play a role in mobilizing basophils, a rare immune cell that plays an important role in the development of allergies. In turn, these basophils also produce another cytokine called interleukin-4 (IL-4), which can reactivate cytotoxic T cells and send them signals to restore and destroy tumors. Researcher Chang said that we had not previously found that basophils were involved in the signaling cascade process of restoring cytotoxic T cells. These findings are preliminary, but targeting tumor-associated basophils represents a very promising way to enhance the body's anti-tumor immunity and improve patient treatment outcomes.
In summary, the results of this study reveal the key role of IL-3-mediated cytotoxic T lymphocyte-basophil crosstalk in regulating the body's anti-tumor immunity. It also shows that the use of IL3 may be a promising means to optimize and enhance the efficacy of cancer immunotherapy.
Reference
Wei J, et al. IL3-Driven T Cell-Basophil Crosstalk Enhances Antitumor Immunity. Cancer Immunology Research, 2024: OF1-OF18.