DNA barcoding reveals the ability of cancer cells to evade immune system defenses

Each colored ribbon represents a DNA barcode
.
As the tumor progresses, some cancer cells begin to dominate the tumor, as indicated by
the orange and red ribbons.
This suggests that these cancer cells already have the ability to escape the immune system and continue to grow
even after treatment.

Using DNA to track the time of cancer cells through barcodes, scientists have shown that cancer cells have different abilities to escape the defenses of the immune system
.

According to a new scientific study from the Gavin Institute for Medical Research, some cancer cells can use parallel mechanisms to circumvent the immune system's defenses and resist immunotherapy treatments
.

The researchers found that breast cancer cells were able to replicate and metastasize
by inhibiting the action of killer T cells and hindering the immune system's ability to mark tumor cells for destruction.

Lead author Louise Baldwin, a PhD student at Professor Alex Swarbrick: "We know that breast cancer generally does not respond well to immunotherapy, and we wanted to know if there is an intrinsic mechanism that enables breast cancer cells to escape the immune system
.
"

For the study, the scientists used a technique called DNA barcoding, which labels cells with known sequences and tracks the development of
tumor cells.

Ms Baldwin said: "We found that there are rare cancer cells that are able to escape the immune system and escape immunotherapy
.
"

These mechanisms can serve as potential targets for therapy, preventing tumor cells from adapting and spreading
.
Another future application could be in terms of prognosis, where a large number of cells may indicate which patients may not respond adequately
to immunotherapy.

The new study was published today (November 7) in the journal Nature Communications
.
In this video, Professor Alex Swarbrick explains the research
.

Although immunotherapy is an effective treatment for many cancers, in some people, cancer cells evolve beyond the defenses of the immune system
.
This process is called immune editing
.
The interaction between tumor cells and immune cells causes many cancer cells to be destroyed by the immune system, but some go undetected and continue to grow and spread
.

The researchers used mouse breast cancer cells labeled with known DNA "barcodes," a sequence
that passes from one generation of cells to the next.

The barcode allowed the team to pinpoint where the more aggressive, resistant cells came from because they traced back to the original cell to see if it grew or shrunk
.

"First author Dr.
Simon Junankar wanted to understand whether resistance is adaptive — whether cancer cells are evasive and roundabout — or whether they pre-programmed to evade the immune system," said
Associate Professor Alex Swarbrick, lab leader and co-leader of Garvan's Cancer Dynamic Cell Ecosystem Project.

The team found that even before treatment, cancer cells had diversified
.
"Some cells have acquired the ability to evade immunity, which means they have an innate ability to
evade the immune system," he said.

Cells seem to complete this process
in parallel.
One way is to inhibit the action of killer T cells, which normally destroy harmful cells
.
The other is to reduce the expression of MHC1 on cells, a marker
for the immune system to recognize harmful cells.

Associate Professor Swarbrick said: "When the immune system is activated, most tumour cells disappear, but a small fraction continue to grow and expand
.
Tumors continue to evolve and diversify, and treatments such as the role of the immune system or chemotherapy are like pruning a tree – the cancer cells are destroyed, but the remaining branches of the tree continue to grow
.
”

The scientists also investigated the genes of these cells, but found no genes
associated with them.
This suggests that epigenetics may be at work
.

Reference: DNA barcoding reveals ongoing immunoediting of clonal cancer populations during metastatic progression and immunotherapy response