Reference News Network, October 29 report. According to the website of Science Daily in the United States, on October 16, scientists have discovered a method to convert refractory tumors into targets for the immune system. They used two protein stimulators to elicit strong responses from T cells and B cells, and established immune structures within the tumor, which can not only improve survival rates but also prevent tumor recurrence. This method can make existing immunotherapies and chemotherapy more durable and effective.

By stimulating two key immune pathways, researchers successfully converted "immune cold" tumors into reactive tumors that the body can attack. This treatment generated persistent immune memory, showing hope for long-term cancer suppression.

Scientists at Johns Hopkins Children's Hospital discovered new evidence through a series of mouse models of breast cancer, pancreatic cancer, and muscle cancer, proving that strengthening the body's natural immune defense can both prevent cancer recurrence and improve survival rates.

This study was recently published in the journal Nature Immunology, funded by the National Cancer Institute/National Institutes of Health, focusing on finding new ways to help the immune system recognize and destroy tumors that usually evade detection.

Many malignant tumors are described as immunosuppressive or "immune cold" because the body's defense system fails to recognize them as threats. Patients with these "cold" tumors often respond poorly to traditional treatments, with unsatisfactory treatment outcomes. The Johns Hopkins research team therefore set out to study how to convert these "immune cold" tumors into "immune hot" tumors, which are more sensitive to attacks by immune cells such as B cells and T cells. This way, the efficacy of chemotherapy and immunotherapy can be greatly enhanced.

Building on previous breast cancer research, researchers proposed that stimulating the tumor environment with immune-activating substances can improve the strength and organization of tertiary lymphoid structures (TLSs), which are specialized centers where immune cells gather and coordinate their attack against cancer.

TLSs are clusters of lymphocytes found in areas of chronic inflammation, including "immune hot" tumors. Their presence is closely related to better treatment outcomes and longer survival times due to their role in coordinating concentrated immune responses.

To validate their idea, the research team reconstructed a tumor environment rich in TLSs to determine which signals triggered the formation of TLSs. Subsequently, they used two immune-stimulating molecules (agonists) to introduce these signals into the tumors of mice lacking TLSs, activating the STING protein and the lymphocyte beta receptor.

When these two proteins were activated simultaneously, the immune system produced a rapid and powerful response. Killer T cells (CD8+ T cells) began to act, suppressing tumor growth, while new high endothelial cell microveins (specialized blood vessels that allow immune cells to enter tissues) began to form. These vessels served as channels, allowing large numbers of T cells and B cells to enter the tumor, organizing themselves into new TLSs.

In these TLSs, B cells initiated a germinal center response, developing into antibody-producing plasma cells and generating persistent memory cells. Researchers also found tumor-specific IgG antibodies and persistent plasma cells in the bone marrow, which are clear signs of a lasting systemic immune defense capable of preventing cancer recurrence.

The treatment also increased helper T cells (CD4+ T) and memory CD8+ T cells, along with balanced immune signals, enhancing both antibody-mediated (humoral) and cell-mediated immunity.

The researchers stated that all these findings indicate that early combined efforts to enhance T cell activity can not only directly kill tumor cells, but also induce the maturation of TLSs, thereby maintaining and enhancing the anti-tumor response.

"The results show that we can effectively induce functional TLSs in immune cold tumors," said Dr. Masanobu Komatsu, the lead researcher and senior scientist at the Institute for Pediatric Cancer and Blood Diseases at Johns Hopkins, "By establishing the correct immune infrastructure within the tumor, we can enhance the patient's own defenses - including T cells and B cells - to combat the growth, recurrence, and metastasis of cancer."

Since the abundance of TLSs is associated with a more optimistic prognosis in many types of tumors, the combined application of these two protein stimulants may provide a broadly applicable method to enhance existing therapies, including checkpoint inhibitors, a pillar of immunotherapy, as well as the effectiveness of traditional chemotherapy.

Dr. Komatsu's team is further investigating the mechanisms of TLSs therapy and preparing for its clinical application in adult and pediatric cancer patients.

This study was supported by an R01 grant from the National Cancer Institute/National Institutes of Health, the Department of Defense Congressionally Directed Medical Research Programs, and the Bankhead-Coley Cancer Research Program of the Florida Department of Health. (Translated by Wenyi)

Original article: https://www.toutiao.com/article/7566609836483084842/

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