Immune System Uses Melanoma's Own Proteins to Kill
Off Cancer Cells, Researchers Say
Transfer of cancer building cells to immune system
provides crucial intelligence about the attacking cancer, which
the right defense to kill the cancer
Feb. 4, 2013 – Researchers have found that the
transfer of a protein that promotes cancer development from melanoma
cancer cells to T cells in the immune system alerts the immune cells of
the danger and allows them to develop the molecules necessary to kill
The small family of proteins, called Ras, controls
a large number of cellular functions, including cell growth,
differentiation, and survival. And, because the protein has a hand in
cellular division, mutated Ras, which can be detected in one-third of
all tumors, contributes to many human cancers by allowing for the rapid
growth of diseased cells.
Now, researchers at Tel Aviv University’s
Department of Neurobiology have found that oncogenic Ras, which promotes
cancer development, can also alert the immune system to the presence of
For the first time, the researchers have shown the
transfer of oncogenic Ras in human cells from melanoma cells to T cells,
which belong to a group of white blood cells that are part of the immune
This transfer allows the immune cells to gather
crucial intelligence on what they are fighting and develop the necessary
cytokines, or signalling molecules, to kill the melanoma cells.
The study was conducted by Prof. Yoel Kloog
of Tel Aviv University's
Neurobiology, along with Dr. Itamar Goldstein
of TAU's Sackler
Faculty of Medicine and the Sheba Medical Center and their
Vernitsky and Dr. Oded Rechavi.
Prof. Kloog suggests that a drug that enhances the
transfer of the oncogene from the tumor to the immune cells is a
potential therapy to augment the anti-cancer immune response. This
research has been published in the Journal of Immunology.
Finding the tipping point
– an intriguing first
Although they found that immune cells often
exchange proteins among themselves, the discovery that melanoma cells
transfer mutated Ras is an intriguing first. And it's this initial
transfer that begins what the researchers call a positive feedback loop.
In the lab, researchers incubated T-cells from
patients with human melanoma cells that had originated from tumors to
track the process of handing-off various proteins. They uncovered a
circuit that runs between the cancer and immune cells. Once the melanoma
cells pass oncogenic Ras to the T-cells, the T-cells are activated and
begin to produce cytokines, which enhances their capacity to kill cancer
As these melanoma cells pass along the mutated Ras,
the immune cells become increasingly active. Eventually, enough
oncogenic material is transferred across the immune cells' threshold,
causing the T-cells to act on the melanoma cells from which the
oncogenic Ras was derived. Ultimately, this transfer tips the scales in
favor of the immune cells, the researchers say.
Exploiting the information
The next step is to develop a therapy that can
enhance the transfer in patients with cancers linked to oncogenic Ras,
says Prof. Kloog. And although their research has so far focused on
melanoma, which is known to elicit the response of the immune system, he
believes that this finding could be applicable to other types of
There is a constant balancing act between cancer
cells and the immune system, says Dr. Goldstein. Under normal
circumstances, the immune system will kill some cancerous cells on a
daily basis. The disease becomes critical when the immune system can no
longer keep cancer cells in check. Although there are many theories as
to how cancer cells break free of this cycle, scientists are still
attempting to discover why this occurs.
Prof. Kloog and Dr. Goldstein expressed hope that
this research leads to a better understanding of how the immune system
"It's a part of the interaction between cancer and the
immune system that is not well known," says Dr. Goldstein. "We are
trying to gather more comprehensive data on all the proteins that are
being passed around, and how this information impacts the immune
system's response to cancer."
Melanoma is the most serious form of skin cancer.
While not the most common skin cancer, melanoma
does cause the most fatalities, and most of these are older people. The
average age of diagnosis is 61. The American Cancer Society estimates that
about 123,000 new cases of melanoma in the US are diagnosed every year,
resulting in approximately 10,000 deaths.
Links to More Archived Stories on Melanoma
Melanoma is a form of cancer that
begins in melanocytes (cells that make the pigment melanin). It may begin in a mole (skin melanoma), but can also begin in other
pigmented tissues, such as in the eye or in the intestines.
About 76,250 men and women (44,250 men and 32,000 women)
were expected to be diagnosed with and 9,180 men
and women to die of melanoma of the skin in 2012.
From 2005-2009, the median age at diagnosis for melanoma of the skin was 61 years of age.
Approximately 0.6% were diagnosed under age 20; 6.8% between 20 and 34; 10.7% between 35 and 44; 18.2%
between 45 and 54; 21.6% between 55 and 64; 18.8% between 65 and 74; 16.7% between 75 and 84; and 6.6% 85+ years of age.
The age-adjusted incidence rate was 21.0 per 100,000 men and women per year.
From 2005-2009, the median age at death for melanoma of the skin was 68 years of age. Approximately 0.1% died
under age 20; 2.6% between 20 and 34; 5.6% between 35 and 44; 13.5% between 45 and 54; 19.9% between 55 and 64; 21.2% between 65
and 74; 24.1% between 75 and 84; and 12.9% 85+ years of age.
The age-adjusted death rate was 2.7 per 100,000 men and women per year. These rates are based on patients who
died in 2005-2009 in the US.
Based on rates from 2007-2009, 1.99% of men and women born today will be diagnosed with melanoma of the skin
at some time during their lifetime. This number can also be expressed as 1 in 50 men and women will be diagnosed with melanoma of
the skin during their lifetime. These statistics are called the
lifetime risk of developing cancer.
Sometimes it is more useful to look at the
probability of developing melanoma of the skin between two age groups. For example,
0.99% of men will develop melanoma of the skin between their 50th and 70th birthdays compared to 0.60% for women
On January 1, 2009, in the United States there were approximately 876,344 men and women alive who had a
history of melanoma of the skin - 427,810 men and 448,534 women.
Couples encouraged to examine each other for
suspicious moles that could be skin cancer. Researchers estimate that 40
– 50% of people in the U.S. who live to age 65 will have nonmelanoma
skin cancer at least once.