Otago University scientists have edged closer to new
therapies to enhance the body's immune response to cancer.
The researchers have uncovered a pathway that alters the
immune response in the spleen and lymph system when faced
with cancerous tumour cells.
The research, just published in American haematology journal
Blood, has identified the pathway, or mechanism used
when cells remove unwanted material in lipid-bound particles
Exosomes are only 1/10,000 of a millimetre in diameter but
are important in immunity as they contain proteins that can
enhance or suppress the immune response against cancer and
have recently been exploited as cancer vaccines.
They have also been implicated in autoimmune diseases.
Lead researcher Associate Professor Alex McLellan, from
Otago's Department of Microbiology and Immunology, said
although the existence of exosomes had been known since the
early 1970s, the fate of the released exosomes in the lymph
system or blood was poorly understood until now.
"We have discovered how exosomes are removed from circulation
or lymph fluid and taken up by the immune system, and how
this uptake system suppresses the immune response to these
circulating particles," he said.
"In a normally functioning body this works in our favour to
prevent autoimmunity, but when cancerous cells are involved
you want to block this pathway to make the immune system more
"Although exosomes are normally removed from circulation
within minutes, we were able to induce strong immune
responses to the exosomes by blocking this uptake system."
The study also was the first to record a circulation half
life for exosomes.
Associate Professor McLellan, doctoral student Sarah
Saunderson and colleagues found that the newly discovered
mechanism uses a receptor called CD169 or sialoadhesin that
was expressed on the lymph node or spleen that recognised
sugars (sialic acids) present on the surface of the exosomes.
In the absence of this uptake mechanism, immune responses
were significantly enhanced in the spleen and lymph nodes.
"This suggests that when vesicle-uptake is working normally,
inappropriate immune responses against self-tissues are
prevented," Associate Professor McLellan said.
"Since tumours are also self-tissue the next application is
to design small molecule inhibitors to block this pathway to
enhance the body's immune response to cancer.
"The work has identified a new pathway of intercellular
communication, a process that has involved seven years of
work in the laboratory, and that has the potential to inform
clinical developments in the fields of autoimmunity and
"This is relevant to all types of cancer that can be
recognised by the immune system, including melanoma, and also
The study was conducted with assistance from the Marsden Fund
and also University of Otago grants.