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Decoded: How Cancer Cells Cripple Immune System

Anti-PD1 therapy blocks interaction between PD-1 -- a protein on the surface of T-cells -- and PD-L1, PD-1's counterpart molecule on tumour cells, thus reinvigorating T-cells and allowing them to unleash killing power on the tumour

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cancer cells
The research offers a paradigm-shifting picture of how cancers take a systemic approach to suppressing the immune system. Pixabay

Researchers have found that cancer cells send out biological “drones” to fight the immune system and survive.

The study showed that cancer cells release “drones” — small vesicles called exosomes circulating in the blood and armed with proteins called PD-L1 that cause T-cells to tire before they have a chance to reach the tumour.

The research offers a paradigm-shifting picture of how cancers take a systemic approach to suppressing the immune system.

In addition, it also points to a new way to predict which cancer patients will respond to anti-PD1 therapy that disrupts immune suppression to fight tumours.

“Immunotherapies are life-saving for many patients with metastatic melanoma, but about 70 per cent of these patients don’t respond,” said Guo Wei, Professor at the University of Pennsylvania.

“These treatments are costly and have toxic side effects so it would be very helpful to know which patients are going to respond,” Wei added.

Cancer
Representational image. Pixabay

Anti-PD1 therapy blocks interaction between PD-1 — a protein on the surface of T-cells — and PD-L1, PD-1’s counterpart molecule on tumour cells, thus reinvigorating T-cells and allowing them to unleash killing power on the tumour.

In the study, published in the journal Nature, the team found that exosomes from human melanoma cells also carried PD-L1 on their surface. Exosomal PD-L1 can directly bind to and inhibit T-cell functions.

Identification of the exosomal PD-L1 secreted by tumour cells provides a major update to the immune checkpoint mechanism, and offers novel insight into tumour immune evasion.

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According to the researchers, exosomes are tiny lipid-encapsulated vesicles with a diameter less than 1/100 of a red blood cell.

Since a single tumour cell is able to secrete many copies of exosomes, the interaction between the PD-L1 exosomes and T-cells provides a systemic and highly effective means to suppress anti-tumour immunity in the whole body. This may explain why cancer patients might have weakened immune system, they noted. (IANS)

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Researchers Discover Balance of Two Enzymes That May Help Treat Pancreatic Cancer

While still in the earliest stages, Newton hoped this information might one day aid pancreatic diagnostics and treatment

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Cancer
Cancer Ribbon. Pixabay

A new research has set the stage for clinicians to potentially use levels of a pancreatic cancer patient’s PHLPP1 and PKC enzymes as a prognostic and for researchers to develop new therapeutic drugs that change the balance of the two enzymes as a means to treat the disease.

The study, published on Wednesday in Molecular Cell, was led by Alexandra Newton, professor in the Department of Pharmacology at the University of California, San Diego, School of Medicine, and Timothy Baffi, a graduate student in her lab, Xinhua news agency reported.

The new study built on the team’s work in 2015 that found the enzyme PKC, which was believed in previous studies to promote tumour growth, actually suppressed it.

The latest study took the investigation a step further by uncovering how cells regulate PKC activity and discovered that any time an over-active PKC is inadvertently produced, the PHLPP1 “proofreader” tags it for destruction.

Cancer patient
Cancer patient.

“That means the amount of PHLPP1 in your cells determines your amount of PKC,” Newton said. “And it turns out those enzyme levels are especially important in pancreatic cancer.”

The team observed 105 pancreatic cancer tumours to analyze the enzyme levels in each one. About 50 per cent of patients with low PHLPP1/high PKC lived longer than five-and-a-half years.

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While still in the earliest stages, Newton hoped this information might one day aid pancreatic diagnostics and treatment.

Pancreatic cancer is caused by the abnormal and uncontrolled growth of cells in the pancreas, a large gland in the digestive system. It typically doesn’t show symptoms in the early stages. Sufferers tend to develop signs, such as back pain and jaundice, when it has spread to other organs. (IANS)