Researchers at the Indian Institute of Science (IISc.) in Bengaluru, along with colleagues, have identified potential blood-based biomarkers that predict disease progression and survival time in people with late-stage brain tumors.
The team included researchers from the Center for Biosystems Science and Engineering (BSSE) at IISc, the Mazumdar Shaw Center for Translational Research and the Mazumdar Shaw Medical Foundation.
They analyzed tumors and blood samples from individuals with gliomas — tumors that form in the brain — to identify surface proteins on immune cells in the blood whose levels were closely linked to tumor progression. This study was published in the medical journal oncoimmunology,
Siddharth Jhunjhunwala, assistant professor at BSSE and senior author of the study, said, “Our pilot study shows that we can potentially use two blood-based biomarkers present in immune cells to identify patients who have a specific may not perform well with treatment strategies.” According to the researchers, such a blood-based testing method could help clinicians better understand disease progression and choose a more effective treatment regimen.
Conventional cancer treatments, such as chemotherapy, are often ineffective in treating these tumors. This has prompted changes to new techniques such as immunotherapy, which involve stimulating our own immune systems to attack tumor cells. However, efforts to use some standard immunotherapies to treat gliomas have had limited success, he explained.
“This led to a specific scientific gap that we were trying to address, which is to understand the immune profile in the tumor microenvironment,” he said.
The team collected blood and tumor samples from patients with grade 3 and grade 4 gliomas, and compared the numbers of specific immune cells called monocytes and neutrophils in these samples.
“Since these are biosamples, they need to be very well preserved and processed without loss of cell viability,” said Jayashree V. Raghavan, PhD student at BSSE and first author of the study. “We had to split the methodology between the two institutions at IISc. and in the lab of the Mazumdar Shaw Foundation. They will do all the processing and determination to maintain the viability of the cells, and then we will do the characterization and immunostaining here.”
The team also looked for differences in the composition of surface proteins on these cells in the two grades of tumors. They found that a certain type of monocytes – M2 monocytes – were present in large numbers in grade 4 tumor samples. Previous studies have shown that high numbers of M2 monocytes are associated with suppression of immune responses, and therefore this finding may help develop new treatment strategies.
“Future studies may focus on developing treatments that reduce the number of M2 monocytes in the tumor microenvironment or alter their functionality,” explained the authors.
The researchers also found that the levels of two surface proteins on neutrophils and monocytes, CD86 and CD63, were closely related in both blood and tumor samples. The presence of higher levels of these proteins on immune cells in other tumors has been previously associated with poor prognosis, or a lower chance of survival, the authors explain. “Our study showed that you don’t need to look for these markers just in the tumor; you may be able to see them just from the blood, and the physician can assess that,” he said.
However, Dr. Jhunjhunwala cautioned that further testing and validation on a large scale is necessary before it can be taken from lab to clinic. “We want to expand our group and test [for] Individuals with stage 3 and stage 4 brain tumors now have only these two markers, and their survival time is followed,” he said.
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