New mechanisms for cancer cells to evade host immune defenses: or hopefully help develop new cancer therapies

We all know that cancer cells are known for spreading genetic confusion, and as cancer cells divide, DNA fragments and even entire chromosomes can repeat, mutate, or become completely missing;
they say the more unstable the chromosomes, the more likely they are that the DNA fragments in those chromosomes will end where they belong, thus escaping outside the nucleosphere and floating in the cytoste.
cells interpret these free fragments as evidence of virus invaders, which may trigger internal alarms and induce inflammation; immune cells travel to tumor site to release defensive chemicals.
mystery that has long existed is why the immune response of cancer cell-induced host bodies does not kill them? 'We don't really understand how cancer cells survive and multiply in inflammatory environments,' said researcher Samuel Bakhoum. 'In this article, we found a special molecule outside cancer cells that destroys warning signs before they reach neighboring immune cells.'
findings may help explain why some tumors do not respond to immunotherapy, and suggest ways to make cancer cells sensitive to immunotherapy. the alarm system studied by
-detecting dangerous DNA researchers is called cGAS-STING, and when DNA from a virus (or unstable cancer cell chromosome) falls into the cytoste, cGAS binds to it to form a compound molecule of cGAMP, which can act as a warning signal;
addition, most cGAMP can move outside the cell and act as a warning signal to adjacent immune cells, activating the STING path path and launching an immune attack response on infected cells.
previous studies have shown that cGAS-STING signals in cancer cells promote their ability to use immune cell characteristics, especially the ability to crawl and migrate, to help cancer cells metaste.
may provide some answers about how cancer cells survive and metases in an inflammatory environment.
In this study, researchers revealed how cancer cells respond to warning signs that activate cGAS-STING release into the environment, and that a scissor-like protein can "tear" these signals, providing a second way for cells to thwart the threat of immune destruction.
This scissor-like protein that covers cancer cells is called ENPP1, and when cGAMP discovers its path outside the cell, ENPP1 shreds it and prevents the signal from reaching the immune cells;
Through a series of experiments in mice with breast, lung and colorectal cancer, the researchers found that ENPP1 acted as a control switch for immune suppression and cancer metastasis in the body, suppressing the immune response and increasing cancer metastasis when turned on, which, if turned off, boosted the host's immune response and reduced metastasis.
, the scientists analyzed ENPP1 in human cancer samples, whose expression was directly related to increased cancer metastasis and increased tolerance to immunotherapy.
Enhance the ability of immunotherapy From a therapeutic point of view, perhaps the most significant finding in this study is that flipping the ENPP1 switch may increase the sensitivity of different cancer types to immunotherapy drugs - checkpoint inhibitors, which are effective in cancer mouse models.
several companies are currently developing drugs to suppress ENPP1 in cancer cells.
researcher Bakhoum said ENPP1 is located on the surface of cancer cells, which may be very fortunate, because it can be a special target to help design and block the progression of cancer cells of new drugs, and ENPP1 is relatively specific, because most tissues of healthy individuals do not become inflamed, so the drug against ENPP1 mainly affects the progression of cancer.
finally, targeting ENPP1 may affect cancer in two different ways, activating STING signals in adjacent immune cells while simultaneously increasing the level of cGAMP outside cancer cells, while also suppressing immunosuppressive adenosine production.
, the researchers achieved the goal of one stone and two birds.
will continue to delve into the latter stages of the study, and they hope to begin phase 1 clinical trials of ENPP1 inhibitors within the next year.
: Jun Li, Mercedes A Duran, Ninjit Dhanota, et al. Metastasis and immune evasion from extracellular cGAMP hydrolysis, Cancer Discovery (2020). doi：10.1158/2159-8290.CD-20-0387 【2】Discovery about how cancer cells evade immune defenses inspires new treatment approach by Memorial Sloan Kettering Cancer Center