- Stem cell transplantation is an
effective treatment for leukemia and other blood cancers, but its success
rates vary from one individual to another.
- The success rates of stem cell
transplants depends on the genetic make up of the proteins inherited.
- The proteins inherited, play an
important role in deciding the activity of the immune system, either by
increasing or reducing the killing of the damaged cells by the immune
The activity of the immune system and the
ability to fight cancer is decided by the body's genetic make up.
The genetic make up decides the type of protein
that the individual inherits. This can influence the risk of certain types of
auto-immune diseases and also the individual's response to cancer
‘Understanding the genetic make of proteins and its influence on the immune system will help in developing better transplant therapy for more people living with blood cancer.’
The study was conducted by a team of researchers
at the University of Birmingham in conjunction with researchers from
Birmingham's Queen Elizabeth Hospital.
The study focuses on a protein called ULBP6.
This protein helps in the removal of damaged cells.
Proteins are made up of organic compounds called
Proteins do most of the work in cells and are
required for the structure, function, and regulation of the body's tissues and
It plays an important role in:
- breaking down food
- growth and repair of body tissue
- Performance of many
other body functions
Lead author of the study Professor Paul Moss
from the University of Birmingham's Institute of Immunology and Immunotherapy,
said "We worked on a protein called ULBP6 which leads to the removal of
damaged cells and an interesting observation has been that there are two types
of this protein found in different people. This is important as previous
studies have shown that the type of protein that we inherit from our parents
can influence our risk of auto-immune disease and affect how we respond to some
forms of cancer treatment."
protein is found on the surface of damaged
cells, including several types of cancer cells.
This protein acts as a 'flag' that signals the
white cells in the immune system to kill the damaged cell.
In the study, the research team found that there
are two major types of the protein that is inherited. People inheriting a
certain subtype have shown poor outcome after stem cell
This procedure also referred to as bone marrow
transplant is used to treat leukemia
Proteins are made up of many smaller units
called amino acids that are attached to one another in long chains. There are a
total of 180 amino acids in the body.
The discovery shows that the two subtypes of the
ULBP6 differ only by two amino acids.
Professor Ben Willcox,
also from the University of Birmingham's Institute of Immunology and
Immunotherapy, said "It has surprised us that this can have such an
important influence on patient outcomes."
Strong Bond with Receptor
The study showed that one form of ULBP6 forms a
very strong bond with its receptor NKG2D on the immune system. This form also
termed as the 'sticky' form binds 10 times more strongly with its receptor.
But the strong bond reduces the killing of the
damaged cells by the immune system, rather than increasing
"In addition, when the protein is released
into the local environment it can act to block the signaling pathway."
This information could be used to improve the
outcome for patients undergoing stem cell transplantation.
Alasdair Rankin, Director of Research at
Bloodwise, said "For some people with leukemia and other types of blood
cancer, stem cell transplantation can mean the difference between life and
death. But a stem cell transplant is a grueling procedure which sadly does not
always work, so we need research to improve success rates."
Though the findings will not help to change the
type of care, it may help us understand why transplants work less well in some
people. This knowledge is important for developing better transplant therapy
for more people suffering from blood cancer.
The study is published in Science
- Amino acids - (https:medlineplus.gov/ency/article/002222.htm)
- Paul Moss et al. A disease-linked ULBP6 polymorphism inhibits NKG2D-mediated target cell killing by enhancing the stability of NKG2D-ligand binding. Science Signaling; (2017) DOI: 10.1126/scisignal.aai8904