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HMGB1 Secretion and Mesothelioma: Immunotherapy Implications

What is Mesothelioma?

Malignant mesothelioma is a fast-moving, proliferous cancer that typically affects the lungs (pleural mesothelioma), heart (pericardial mesothelioma) or abdominal cavity (peritoneal mesothelioma), and in very rare cases, the testicles. It is a very uncommon form of cancer, and it is typically associated with long-term exposure to asbestos-containing materials. Thus, many of the victims of mesothelioma are people who spent a lifetime working in the construction industry, installing asbestos-containing tiles and insulation. The time from initial exposure to diagnosis is incredibly long as compared with other cancers, and sometimes a person who is afflicted with mesothelioma may not notice the symptoms until several decades down the road.

What is Immunotherapy?

Immunotherapy is an up-and-coming, cutting-edge line of treatment for cancer wherein the power of the body’s own autoimmune response is used to “attack” malignant cells, such as those that amass in mesothelioma. Some types of immunotherapy involve vaccination (although little research is currently focused on cancer vaccines), while others utilize manipulation or introduction of antibodies into the body. In one form of immunotherapy, laboratory-made antibodies are introduced to a cancer patient’s body, and these antibodies can then travel to the site of the cancer itself, attacking the malignant cells in order to eradicate the cancer or at least stop it from metastasizing and spreading further.

What is HMGB1?

HMGB1 is an acronym for “high mobility group protein B1” (also known as amphoterin). HMGB1 is a protein that human bodies secrete in response to nearby inflammation. Heightened levels of HMGB1 are often indicative of autoimmune dysfunction such as that caused by lupus, arthritis, and cancer—malignant mesothelioma in particular. Not only is HMGB1 more prominently present in mesothelioma patients, it also appears to play a role in keeping the cancer “up and running.”

What Happens with HMGB1 in Mesothelioma Patients?

HMGB1 is secreted at a higher level in mesothelioma patients than in people without mesothelioma. When researchers initially made this discovery, the high levels of the protein were thought to merely be a response by the body’s immune system to the presence of cancer—that is, that the cancer caused the excessive release of the HMGB1 protein. However, recent research has shown a connection between HMGB1 secretion and cancer progression—that is, that the HMGB1 appears to “feed” the malignant cells. So, not only is it a case of HMGB1 increasing as the cancer spreads, but the HMGB1 also appears to aid the spread of the cancer itself in a “symbiotic” feedback loop of sorts. In other words, HMGB1 isn’t simply secreted in response to the cancerous growth—it enhances cancerous growth.

Research Findings and Implications

Recent studies conducted by Dr. Haining Yang of the University of Hawaii Cancer Center and her team of researchers from all over the globe discovered that manipulation of HMGB1 via immunotherapy methodology has an impact on the spread of malignant mesothelioma cancer. They found that, rather than HMGB1’s increased presence in the body simply being a result of the cancer itself, HMGB1 appears to actually increase the proliferation and spread of cancer cells. Thus, when HMGB1’s production is inhibited through the use of lab-created antibodies, the spread of mesothelioma can also be inhibited.

Dr. Yang’s team also found that the cancer cells created by mesothelioma need HMGB1 to migrate, and even to “survive,” and therefore, when these malignant cells are deprived of HMGB1 via use of immunotherapy, they are unable to spread any further and even die off. By targeting the HMGB1 and stopping its production, the mesothelioma itself is also being targeted and stopped. In Dr. Yang’s study, mice which were successfully treated with HMGB1 inhibition therapy saw their tumor growth stop, and they lived longer compared with mice whose HMGB1 levels were left alone.

What This Means for the Future of Mesothelioma Treatment

Mesothelioma is aggressive—it moves quickly, and thus, it can have devastating consequences if it is not caught very early on. Unfortunately, many people do not notice the signs and symptoms of mesothelioma until it has already spread and done a great deal of damage to their bodies. This is why early diagnosis and effective treatment are crucial for mesothelioma patients.

Although it may not completely eradicate the cancer, use of HMGB1-inhibiting antibodies in immunotherapy could help people suffering with malignant mesothelioma cancer to live longer lives by causing the cancer cell growth to halt in its tracks. Preventing metastasis—wherein the cancer travels from its original location in the heart, lungs or chest cavity to far-off organs in other parts of the body—is key in creating a better prognosis for those diagnosed with mesothelioma. If this relatively-new treatment is fully implemented, the millions of people now suffering with mesothelioma could see their life expectancies lengthened considerably.

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