Immunotherapies have the power to harness the body’s own immune system to eliminate tumours. Past consideration for immunotherapy in brain tumour treatment was limited due to the notion that the immune system was excluded from brain. It is now accepted that the central nervous system undergoes constant immune surveillance. A reassessment of basic neuroimmunology in the context of brain cancer is warranted to further investigate the potential for immunotherapies to be used in brain tumour treatment. To address this, we have investigated an anti-tumour immune response using a model of melanoma metastases in the brain.
Ovalbumin (Ova)-expressing B16 melanoma cells were intracranially implanted into immune competent C57BL/6 mice. Using flow cytometry we investigated the activation of Ova-specific T cells that had been adoptively transferred to tumour-bearing mice. Measuring CD69 as a marker of T cell activation showed that activation of Ova-specific T cells occurred in superficial and deep cervical lymph nodes, but not in the spleen, brain, or distal lymph nodes. To further investigate how activation of these T cells was achieved, brain melanomas were established in mice lacking the C-C chemokine receptor type 7 (CCR7), which is known to be required for migration of antigen presenting cells to lymph nodes, where they activate T cells. Surprisingly, deletion of CCR7 had no effect on activation of Ova-specific T cells. These data imply that while immune surveillance of brain tumours occurs in our model, the mechanisms are distinct from known immune activation events in skin.
Improving our understanding of these mechanisms may lead to the development of novel immunotherapies to improve patient outcomes. Future studies will establish how brain tumour antigen reaches tumour-draining lymph nodes to mediate anti-tumour T cell immunity. Moreover, these mechanisms will be investigated in other brain cancer models, such as medulloblastoma.