Researchers at the Indian Institute of Science (IISc.) in Bengaluru, along with collaborators, have identified potential blood-based biomarkers to predict disease progression and survival times in those with late-stage brain tumour.
The team included researchers from the Centre for BioSystems Science and Engineering (BSSE) at IISc., the Mazumdar Shaw Center for Translational Research and Mazumdar Shaw Medical Foundation.
They analysed tumour and blood samples from individuals with gliomas – tumours that occur in the brain – to identify surface proteins on immune cells in the blood whose levels were closely linked to tumour progression. This study was published in medical journal OncoImmunology .
“Our pilot study suggests that we can potentially use two blood-based biomarkers present in immune cells to identify patients who might not perform well with particular treatment strategies,” said Siddharth Jhunjhunwala, Assistant Professor in BSSE, and senior author of the study. Such a blood-based testing methodology could help clinicians better understand disease progression and choose a more effective treatment regimen, according to the researchers.
Conventional cancer treatment, like chemotherapy, is often ineffective in treating these tumours. This has prompted a shift to newer techniques like immunotherapy, which involves provoking our own immune system to attack the tumour cells. However, attempts to use some of the standard immunotherapies to treat gliomas have met with 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 tumour microenvironment,” he said.
The team collected blood and tumour 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.
“Because these are biosamples, they need to be preserved and processed very well without loss of cell viability,” explained Jayashree V. Raghavan, PhD student at BSSE and first author of the study. “We had to split up methodology between two institutes — at IISc. and at the lab in the Mazumdar Shaw Foundation. They would do all the processing and fixation to retain the viability of the cells, and then we would do the characterisation and immunostaining here.”
The team also looked for differences in the composition of surface proteins on these cells across the two grades of tumours. They found that a certain type of monocytes — the M2 monocytes — were present in larger numbers in the samples from Grade 4 tumours. Previous studies have shown that high numbers of M2 monocytes are associated with a suppression of immune responses, and this finding could therefore help develop new treatment strategies.
“Future studies could focus on developing therapies that reduce the numbers of M2 monocytes in the tumour microenvironment or alter their functionality,” the authors explained.
The researchers also found that levels of two surface proteins on neutrophils and monocytes, CD86 and CD63, were closely related in both the blood and tumour samples. The presence of high levels of these proteins on immune cells in other tumours has previously been associated with poor prognosis, or low chances of survival, the authors point out. “What our study showed is that you do not need to look at these markers only in the tumours; you might be able to look at these just from the blood, and the clinician can make an assessment,” they said.
Dr. Jhunjhunwala cautioned, however, that further testing and validation on a larger scale is necessary before this can be taken from the lab to the clinic. “We would like to expand our cohort and test [for] only these two markers now, in individuals with Stage 3 and Stage 4 brain tumours, and follow their survival times,” he added.
