In 2018 in the United States about 23,880 individuals will be diagnosed with malignant tumors of the brain or spinal cord, with 16,830 individuals dying from a brain or spinal cord tumor. A recent study published in Nature Medicine reveals how brain cancers escape detection by the immune system by inhibiting and trapping T-cells in bone marrow. When it comes to brain cancers low numbers of immune system T cells in the blood is not uncommon, this can be a side effect of cancer treatments.
Many different types of brain tumors exist, they may be benign or malignant as well as originating in the brain or spread from other parts of the body. The growth rate of brain tumors can vary as well as the location in the brain; these two factors can influence how it may affect the function of your nervous system. Symptoms typically include headaches, nausea, vision problems, speech difficulties, confusion, and behavior changes among many other things. Risk factors can include exposure to radiation as well as family history of brain tumors or genetic syndromes. Treatment can vary based on the type of brain tumor as well as the size and location but may include chemotherapy or immunotherapy.
Researchers from the Osaka University, as well as other institutions, studied T cells levels in patients with brain cancers. Imaging results and blood tests of patients were analyzed, even before being treated. Despite the low T cell levels, they found that patients had contracted spleens indicating that the T cells are not sequestered in the spleen. Similar results were seen in mice, but upon examination of bone marrow, a significant expansion of T cell numbers was seen in the mice. When the bone marrow of human patients was examined a similar phenomenon was observed, T cells that would usually attack the tumor are trapped in the bone marrow.
Using flow cytometry, they found an inverse relationship between T-cell surface protein S1P1 levels and T-cell numbers in the bone marrow. Protein S1P1, known as Sphingosine-1-phosphate receptor 1, is involved in immune cell regulation and development specifically suppression of innate immune response from T cells. The S1P1 protein is needed for T-cells to leave the bone marrow as well as the spleen, thymus, and lymph nodes. It appears that based on the study brain tumors prevent T cells from leaving the bone marrow by lowering levels of protein S1P1. Researchers found that the T cells can be freed by blocking internalization of S1P1 allowing the T cell to emerge from the bone marrow.
"We expect these results to provide clues that will help improve the effects of immunotherapy treatments for brain tumors," says coauthor Shohei Koyama. "It should be possible to induce these trapped T lymphocytes to migrate and attack the tumor." Therapies that focus on activating these T cells may be useful adjuncts to current treatments for brain cancers.
To learn more about T cells and how they interact with cancer cells watch the video below!