Innovative Immune System Enhancement Shows Promise in Cancer Treatment
Researchers from Johns Hopkins All Children's Hospital have uncovered promising findings regarding a novel method to enhance the immune system's ability to combat cancer. This breakthrough, published in Nature Immunology, focuses on the transformation of immune-cold tumors--those that evade detection by the immune system--into immune-hot tumors, which actively engage immune cells to attack cancer cells.
Malignant tumors often suppress the immune response, resulting in poor responses to standard therapies and unfavorable patient outcomes. The study aims to convert these immune-cold tumors into immune-responsive environments where immune cells, including T and B cells, can effectively target and eliminate cancer cells. Building on previous research, the team hypothesized that enhancing the tumor microenvironment with immune-activating agents could improve the formation and function of tertiary lymphoid structures (TLS), which play a crucial role in facilitating immune responses against tumors.
Tertiary lymphoid structures are clusters of immune cells that develop in response to chronic inflammation, and their presence is strongly associated with better treatment outcomes and increased survival rates among cancer patients. To explore their potential, the researchers employed a strategy to stimulate the formation of TLS in tumors lacking these structures. They introduced two immune-activating agents that target the STING protein and the lymphotoxin-? receptor (LT?R).
The combined activation of STING and LT?R resulted in a swift immune response characterized by an increase in killer T cells (CD8+ T cells), which significantly inhibited tumor growth. Furthermore, this dual activation led to the development of high endothelial venules, specialized blood vessels that facilitate the entry of lymphocytes into tissues. This process created pathways for a large influx of T and B cells into the tumors, allowing them to assemble into functional TLS.
Within these structures, B cells underwent germinal-center reactions, maturing into antibody-secreting plasma cells and generating long-lived memory cells. The presence of tumor-specific IgG antibodies and the persistence of plasma cells in the bone marrow were indicative of a robust and lasting immune response capable of preventing cancer recurrence.
Additionally, the treatment promoted an increase in helper (CD4+) T cells and memory CD8+ T cells, contributing to balanced immune signaling and enhancing both humoral and cell-mediated immunity. The researchers concluded that early and combined efforts to stimulate T-cell activity not only directly target cancer cells but also promote the maturation of TLS, sustaining and amplifying anti-tumor immune responses.
The lead investigator, Masanobu Komatsu, Ph.D., emphasized the potential of this approach, stating that by creating a favorable immune environment within tumors, it is possible to strengthen the patient's immune defenses against cancer progression, relapse, and metastasis. Given that TLS abundance correlates with improved clinical outcomes across various tumor types, the dual stimulation method could represent a widely applicable strategy to enhance the efficacy of existing cancer treatments, including immunotherapies and conventional chemotherapy.
The research team is currently investigating the mechanisms underlying TLS therapy and is preparing for clinical trials to assess its applicability in both adult and pediatric cancer patients.