Amazing stuff! Cancer is history (soon)! Skull bones can fight brain cancer? The brain is not as immune-privileged as was previously assumed!
"The discovery of tumour-reactive T cells in the skulls of people with brain cancer has challenged the idea that the brain has minimal immune-cell activity. Nineteen people with glioblastoma were injected with a radioligand that marked out immune cells during a PET scan. Their skulls were found to have more immune cells than a control group of six people with a non-malignant brain disease. Skull fragments removed during surgery to treat glioblastoma were found to contain T cells that recognised brain-cancer cells and killed them in laboratory experiments. These T cells also expressed high levels of the S1PR1 protein that encourages immune cells to infiltrate tumours. “These features suggest that the skull bone might serve as a reservoir, providing tumour-reactive T cells that migrate to tumour sites,” ..."
"The human brain is usually considered to be beyond the reach of most immune cells. However, analysis of people who have brain tumours has revealed tumour-targeting T cells of the immune system in skull bones near the cancer site.
The brain has historically been considered to be immune-privileged, meaning that few immune cells reside in or infiltrate the brain, even in the case of disease. This lack of immune cells has made it hard to develop therapies that use a person’s own immune system to identify, attack and eradicate brain tumours. ..."
From the abstract:
"The ecosystem of brain tumors is considered immunosuppressed, but our current knowledge may be incomplete. Here we analyzed clinical cell and tissue specimens derived from patients presenting with glioblastoma or nonmalignant intracranial disease to report that the cranial bone (CB) marrow, in juxtaposition to treatment-naive glioblastoma tumors, harbors active lymphoid populations at the time of initial diagnosis. Clinical and anatomical imaging, single-cell molecular and immune cell profiling and quantification of tumor reactivity identified CD8+ T cell clonotypes in the CB that were also found in the tumor. These were characterized by acute and durable antitumor response rooted in the entire T cell developmental spectrum. In contrast to distal bone marrow, the CB niche proximal to the tumor showed increased frequencies of tumor-reactive CD8+ effector types expressing the lymphoid egress marker S1PR1. In line with this, cranial enhancement of CXCR4 radiolabel may serve as a surrogate marker indicating focal association with improved progression-free survival. The data of this study advocate preservation and further exploitation of these cranioencephalic units for the clinical care of glioblastoma."
Surprising finding in glioblastomas: Islands of potent immune cells in the local bone marrow (original press release) "Glioblastomas are highly aggressive, usually incurable brain tumors. If all therapeutic options are exhausted, patients have an average life expectancy of less than two years. Now researchers from the German Cancer Consortium (DKTK) at the West German Tumor Center Essen have made a surprising discovery: in the vicinity of glioblastomas, they found islands of highly potent immune cells in the neighboring bone marrow of the skull, which play a central role in defending against cancer. The new data may open up prospects for innovative therapies. On the other hand, they cast a shadow over conventional strategies."
Immunotherapy often doesn’t work against glioblastoma, but T cells inside skull bones might form the basis for new therapies.
Skull bone (gray) of a patient with glioblastoma. Vessels (red) in the inner cavities of the local bone marrow; the immune cells, which are only found enriched in the immediate vicinity of the tumor, are shown in green.
Fig. 1: Glioblastoma-associated enrichment of immune cells in the CB [cranial bone].
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