Although immune checkpoint inhibitors can effectively reactivate tumor immunity in some cancer types, many other solid tumors, including breast cancer, may be largely unresponsive, and understanding the mechanisms by which these non-responsive cancers evade immunity and whether this occurs at the clonal level may help researchers improve the design of
immunotherapies 。 Recently, a study entitled "DNA barcoding reveals ongoing immunoediting of clonal cancer populations during metastatic progression and immunotherapy response" published in the international journal Nature Communications, Scientists from the Gavin Institute of Medical Research in Sydney and other institutions have found that certain cancer cells may deploy parallel mechanisms to evade the defenses of the host body's immune system and help defend against immunotherapy
By inhibiting the activity of killer T cells and blocking the immune system's ability to label tumor cells for destruction, breast cancer cells may be able to replicate and metastasize
。 Lead author Dr.
Louise Baldwin said that we all know that breast cancer does not usually respond to immunotherapy, so we wondered if there is an internal mechanism that motivates breast cancer cells to avoid attack by the host body's immune system, so the researchers used a technique called DNA barcoding to mark cancer cells with a known sequence and track the progress of tumor cells over time
Researchers have found that there may be some rare cancer cells that can evade the attack of the body's immune system and immunotherapy; This mechanism may be used as a potential target to help develop new therapies that block the adaptation and spread of tumor cells, while another future application is in terms of patient prognosis, where the presence of a large number of cancer cells may indicate which patients do not respond
to immunotherapy 。 Although immunotherapy can be used as an effective treatment for many cancers, in some people, the body's cancer cells may evolve beyond the body's immune system defenses, a process called immunoediting, that is, the interaction between tumor cells and immune cells will cause many cancerous cells to be destroyed by the immune system, but also leave some undetected cancer cells, which will continue to grow and spread
The use of DNA barcoding technology may reveal the ability of cancer cells to
evade attacks by the host body's immune system.
Image source: Nature Communications (2022).
The researchers then used mouse breast cancer cells labeled with a known DNA barcode that can be passed from one mouse generation to the next; Therefore, the barcode can help researchers see where the more aggressive and tolerant cancer cells come from, because it can help trace back to the original cell to see whether it continues to grow or is already shrinking and filling
Researcher Simon Junankar points out that we want to study whether this tolerance is adaptive (whether cancer cells dodge) or whether it can be pre-programmed to evade the host body's immune system
The researchers found that even before treatment, cancer cells had diversified characteristics, and some of them had acquired the ability to avoid the epidemic, which means that they have an innate ability to
evade the host body's immune system.
These cells appear to do this in parallel, one way is to inhibit the activity of killer T cells (which normally destroy harmful cells), and on the other hand, to reduce the expression of MHC1 molecules on the cell surface, which acts as a marker
for the immune system to recognize harmful cells.
When the immune system is turned on, most tumor cells disappear, but only a small percentage continue to grow and expand
Tumor cells evolve and become diverse, and the activity of the immune system and treatments such as chemotherapy are like pruning trees, cancer cells are destroyed, but the remaining branches on the tree continue to grow; In addition, the researchers also analyzed the genetic characteristics of the cells, but did not find any relevant genes, which may suggest that epigenetic factors may play an important role
in the escape of cancer cells.
, Bartonicek, N.
, Yang, J.
DNA barcoding reveals ongoing immunoediting of clonal cancer populations during metastatic progression and immunotherapy response.
Nat Commun 13, 6539 (2022).