Dysfunctional cells, for instance, cancer, are destroyed by the immune system automatically; nonetheless, cancerous cells mostly survive through it. A new study by the research team at the Salk Institute demonstrates one approach by which the rapidly developing tumors escape anti-tumor immunity. The scientists exposed 2 gene-regulating molecules that change the cell signaling in tumor cells to stay alive and weaken the normal immune response of the body. The findings can someday pinpoint to a new target for treatment of several types of cancer.
Professor Juan Carlos Izpisua Belmonte said, “The immunological pressure stirring during tumor development might be damaging for the tumor to grow. Nevertheless, the cancer cells uncover a means to escape such a circumstance by off-putting the anti-tumor immune response.”
Often, cancerous tumors develop so rapidly that they utilize their obtainable blood supply, generating a low-oxygen situation known as hypoxia. Generally, cells begin to self-destruct in hypoxia, however, in few cancers, the microenvironment neighboring the hypoxic tumor tissue has been discovered to assist in protecting the tumor.
Izpisua Belmonte said, “Our results actually specify how cancer cells react to a varying microenvironment and hold back anti-tumor immunity via intrinsic signaling.” The answer was via microRNAs.
MicroRNAs—small, non-coding, molecules of RNA that control genes by RNA silencing—have been progressively involved in survival and development of tumors. To better comprehend the relation between tumor survival & microRNAs, the team analyzed diverse tumor types for distorted microRNAs levels. Two microRNAs, namely, miR93 & miR25, were recognized whose levels elevated in hypoxic tumors.
The microRNA levels were then assessed by the team in tumors of cancer patients (n=148) and discovered that tumors with elevated levels of miR93 & miR25 resulted in worse prognosis in comparison to tumors of patients with lower levels. The opposite was true for another molecule known as cGAS—low cGAS levels in a tumor signify a worse prognosis for the individual.
Using tissue samples & mouse models, the team established that a low-oxygen state stimulated miR93 & miR25 to start a sequence of cell signaling that eventually lowered the levels of cGAS. If miR93 and miR25 were inhibited in the tumor cells by the researchers, then the levels if cGAS remained elevated in the hypoxic tumors.
Thus, recognizing miR93 & miR25 might assist researchers to find a good target to attempt to increase the levels of cGAS and block tumor dodging of the immune response. Nevertheless, the team states targeting microRNA directly in treatment can be fiddly. Targeting the intermediary components in the signaling amid the 2 microRNAs and cGAS might be easier.