Blocking copper uptake in tumor cells may be clue to boosting immune
system

Date:
August 19, 2020
Source:
Children's Cancer Institute Australia
Summary:
Researchers have discovered that removing copper from the blood
can destroy some of the deadliest cancers that are resistant to
immunotherapy using models of the disease.



FULL STORY ========================================================================== Australian researchers have discovered that removing copper from the
blood can destroy some of the deadliest cancers that are resistant to immunotherapy using models of the disease.


========================================================================== While immunotherapy, a treatment that works through a patient's immune
system to kill the cancers, has proven to be a breakthrough for many
cancer patients, offering real hope and for some even a cure -- some
cancers camouflage themselves from current immunotherapies by expressing
the aptly titled Programmed Death Ligand or PD-L1.

Dr Orazio Vittorio and his team from Children's Cancer Institute in
Sydney and UNSW Sydney published the findings today in the journal
Cancer Research.

It is known that cancer cells such as brain cancer "feed" on copper,
often having up to six times the normal levels of the metal inside the
tumour cells.

Dr Vittorio and colleagues, including Professor Maria Kavallaris AM,
studied tumour samples from more than 90 patients with neuroblastoma and
90 patients with gliomas. Both these cancers have high mortality rates
and to date have not responded well to cancer immunotherapy. Neuroblastoma accounts for 15% of total childhood cancer deaths and only 50% of patients
with high-risk neuroblastoma patient survive their disease. Glioblastoma
has the worst survival rate of all cancers, with only 5% of patients
surviving 5 years past their diagnosis.

According to Dr Vittorio, these two cancers express PD-L1 as a way to hide
from the immune system, explaining why these two cancers are so deadly.

By looking at the human biopsies the researchers found a correlation
between high levels of copper and increased expression of PD-L1. The researchers then showed for the first time that copper levels could
control the expression of PD-L1 in cancer cells.

The researchers went on to use an analogue of a drug, called TETA,
that is currently used in the treatment of Wilson's Disease, which is a
rare genetic disorder characterized by excess copper stored in various
body tissues. They used this drug in animal models of neuroblastoma
and glioblastoma to reduce the amount to copper in the tumour cells,
leading to a reduction in the expression of PD-L1.

"When these mice were given immunotherapy there was a significant
reduction in the size of their tumours," Dr Vittorio said.

"Given that TETA is already in use in a number of clinical conditions
and it is inexpensive and easy to manufacture, this may offer a
viable treatment alternative for those cancers that are resistant to
current immunotherapies." Neuroblastoma claims more lives of children
younger than five than any other cancer. Children like Luciano who was diagnosed at 14 months, endured three operations and eight rounds of chemotherapy. ''We are lucky because he responded well to treatment,
but there were so many kids who have been lost.

This research will help give hope to more families and children in the
future'' his mother Maria said.


========================================================================== Story Source: Materials provided by
Children's_Cancer_Institute_Australia. Note: Content may be edited for
style and length.


========================================================================== Journal Reference:
1. Florida Voli, Emanuele Valli, Luigi Lerra, Kathleen Kimpton,
Federica
Saletta, Federico M. Giorgi, Daniele Mercatelli, Jourdin
R.C. Rouaen, Sylvie Shen, Jayne E. Murray, Aria Ahmed-Cox, Giuseppe
Cirillo, Chelsea Mayoh, Paul A. Beavis, Michelle Haber, Joseph
A. Trapani, Maria Kavallaris, Orazio Vittorio. Intra-tumoral
copper modulates PD-L1 expression and influences tumor
immune evasion.. Cancer Research, 2020; canres.0471.2020 DOI:
10.1158/0008-5472.CAN-20-0471 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/08/200819094758.htm

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