03:34am Wednesday 18 October 2017

Missing immune response may prove a vital link for new leukaemia treatments

The discovery may even eventually leadto a vaccination against leukaemia for at risk groups who are found to belacking the necessary immune response – meaning that individuals may then relyon their immune system to kill cancerous cells before the disease takes hold.

Cell growth and survival are controlledby complex signalling pathways, but in cancer cells these signals have goneawry. The signals are transmitted using protein modifications, such as adding aphosphate group. This modification is retained when the proteins are broken upinto fragments, called peptides, and presented on the cell surface forinspection by immune cells (T cells). This results in the presentation ofphosphopeptides by leukaemia cells, enabling them to be recognised as abnormalby the immune system.

The Birmingham researchers identified 95phosphopeptides from leukaemia samples, taken directly from patients. 

They went on to show that healthy peopleexhibited an unexpected immune response, with T-cells that recognised thesephosphopeptides, and that this response was lacking in patients withleukaemia. 

When leukaemia sufferers were given astem cell transplant, there was a dramatic recovery of this response andT-cells recognising phosphopeptides-were able to kill leukaemia cells in thelab.

The researchers concluded thatphosphopeptides may therefore be the target of cancer immune surveillance inhumans – giving rise to the possibility of new treatments, which includeengineering T-cells outside of the body to equip them with the immune responseneeded to fight the leukaemia, before putting them back into the patient.

The discovery also gives rise to thepossibility of screening people to see if they have the immune response – thosewho do not may be at risk of developing leukaemia, and a vaccination could evenbe developed to protect these people with the necessary immune response.

Dr Mark Cobbold, from the School ofImmunity and Infection at the University of Birmingham, said: “This is thefirst study to identify phosphorylated tumour antigens that are present onpatient tumour samples and also the first study to look at immune responses tothis new group of antigens in humans. 

“We were surprised to see that healthyindividuals had immunity to these antigens. It could be that just as our immune system fights off infections on adaily basis, it is also fighting cells that develop mutations that could leadto cancer. 

“As we enter old age these responsescould wane and this would explain why, just as older people get more seriousinfections due to impaired immunity, older people are also at greater risk fromcancer.  

“These findings need to be confirmed byother research groups, but could lead to new treatment options for patientswith leukaemia or other cancers or preventative vaccination for at-riskgroups.”

Professor Chris Bunce, Research Directorat Leukaemia & Lymphoma Research, which part funded the study, said: “Stemcell transplants can offer leukaemia patients the chance of a complete cure butthey are not always successful and can have severe side-effects.  By pinpointing key antigens, some of whichare found only on the surface of leukaemia cells, this research could lead tonew ways of modifying patients’ own immune systems to attack only leukaemiacells or even stop them from developing in the first place.”

The research MHC Class I-AssociatedPhosphopeptides Are the Targets of Memory-like Immunity in Leukemia ispublished online in Science Translational Medicine today. Thework was funded by Leukaemia & Lymphoma Research and the Kay Kendal LeukaemiaFund.

Notes to editors

 

Dr Mark Cobbold is available forinterview. Contact Kara Bradley, University of Birmingham press office, 0121414 5134 or 07789 921163 for more information.


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