Cytotoxic T-cells Revitalized in Tumor Microenvironment

By Nithya Somarapu on June 14, 2024

Microscopic view of cytotoxic T-cells interacting with tumor cells in the tumor microenvironment.

The tumor microenvironment, sometimes called the ecosystem surrounding a tumor, comprises blood vessels, tissues, Cytotoxic T-cells, and other immune cells that interact with the tumor and each other. The tumor gradually shapes this environment to suit its needs, monopolizing all the nutrients and providing protection from the immune system. Researchers at The Jackson Laboratory have discovered the cascade of molecules that helps coordinate the attack by two immune cells in their quest to understand the ecosystem’s involvement in cancer risk, development, and treatment.

Led by JAX Assistant Professor Chih-Hao “Lucas” Chang, Ph.D., the research focuses on cytotoxic T-cells, a subset of immune cells that may fight off bacterial infections and other diseases in addition to eliminating virus-infected cells. They target cancerous cells as well. Most malignant cells are removed from our bodies by our immune systems before they have a chance to create any issues. However, given the hostile tumor microenvironment, cytotoxic T-cells get “exhausted” after a tumor becomes established, making them less efficient in attacking malignancies. Chang and associates are looking at the reasons behind these immune cells’ exhaustion as well as possible strategies to induce them to start focusing on tumors again.

“T-cells are excellent at identifying and attacking cells that become cancerous, but they can become exhausted in the tumor microenvironment; they can become overworked and overstimulated, while also being starved of glucose and other nutrients by tumor cells. Helping these cells to function better could improve cancer treatment strategies, particularly immunotherapies,” said Chang, whose work appears in Cancer Immunology Research.

Prior research has demonstrated that cytotoxic T-cell activation results in the release of cytokines, which are signaling molecules. Chang et al. concentrated on one of these cytokines, interleukin-3 (IL-3), and found that cytotoxic T-cells gradually lose their capacity to produce IL-3 within the tumor microenvironment as the tumor grows. Chang then noticed powerful anticancer effects when he increased IL-3 levels in mice with lymphoma or melanoma tumors.

Chang’s group also discovered that basophils, an uncommon immune cell that may also be involved in allergies, are activated by IL-3. These basophils then go on to make interleukin-4 (IL-4), another cytokine that tells cytotoxic T-cells to start looking for and eliminating tumors again.

Basophils have not previously been implicated in the signaling cascade for reinvigorating cytotoxic T-cells. These findings are preliminary, but targeting tumor-associated basophils represents a promising avenue for enhancing antitumor immunity and improving patient outcomes.” – Chih-Hao “Lucas” Chang, Ph.D., JAX Assistant Professor

For more information: IL3-Driven T Cell–Basophil Crosstalk Enhances Antitumor Immunity, Cancer Immunology Research, https://doi.org/10.1158/2326-6066.CIR-23-0851

Nithya Somarapu

With a deep fascination for the intricacies of the medical field, Nithya excels at translating complex medical information into clear and engaging content. Her passion for clear communication fuels her ability to craft compelling narratives for a diverse audience. Nithya's meticulous research ensures the accuracy and depth of the content she creates, empowering readers to stay informed about important medical advancements.