Cancer: How early-stage cells evade the immune system

Evan Walker
Evan Walker TheMediTary.Com |
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  • Researchers are reporting that some early-stage cancer cells activate a gene that helps hide them from the body’s immune response.
  • They say that identifying this uptick in gene expression among cancer cells could lead to new pathways for early diagnosis and future treatment of colon cancer.
  • Experts say more research is needed, however, to confirm these findings and explore new potential therapies and treatments.

Early-stage colon cancer cells use special strategies to evade the body’s natural immune responses to become larger tumors, according to a new study from the Massachusetts Institute of Technology and the Dana-Farber Cancer Institute.

At the most fundamental level, cancer is what happens when cell division runs amok and cells grow uncontrollably.

One of the jobs of the body’s immune system is to recognize and remove these abnormal cells before they proliferate too much.

Identifying where the immune system falters in handling cancerous cells, therefore, is one of the most important areas of study for future cancer treatment and one of the targets of next-generation cancer drugs.

Looking at colon cancer tumors implanted in mice, the researchers found early-stage cancer cells produced and activated a gene called SOX17, which helps hide these cells from the immune system.

In addition, they said SOX17 activation ensures cells will produce fewer molecules called MHC proteins, which are proteins that ensure cancer-associated antigens are visible to the immune system. SOX17 can also stop the production of key receptors that would instruct the immune system to order these cancerous cells to self-destruct.

“Activation of the SOX17 program in the earliest innings of colorectal cancer formation is a critical step that shields precancerous cells from the immune system. If we can inhibit the SOX17 program, we might be better able to prevent colon cancer, particularly in patients that are prone to developing colon polyps,” said Dr, Omer Yilmaz, a study author and an MIT associate professor of biology and a member of MIT’s Koch Institute for Integrative Cancer Research, in a press release.

The scientists also found that as these colon cancer cells grew into larger tumors and metastasized to other organs, the expression of SOX17 was diminished.

“This is a very important study because it provides insight into what triggers early colon cancer to develop and the importance of the protective effect of the immune system,” said Dr. Anton Bilchik, a surgical oncologist and chief of medicine and director of the Gastrointestinal and Hepatobiliary Program at Providence Saint John’s Cancer Institute in California.

“Cancer research is rapidly evolving to improve our understanding of what causes cancer cells to form and then grow,” Bilchik, who wasn’t involved in the study, told Medical News Today. “This is particularly important since most cancers do not have a clear cause and cancer continues to be the Health and Human Services" rationale="Governmental authority">second leading cause of death in the U.S. This study provides not only a pathway for cancer development but also potential targets for diagnosis and treatment.”

This research specifically looked at colon cancer cells and is not generalizable to all cancers, which encompass a host of mechanisms of action of uncontrolled cell division.

In some cases, as with leukemia, cancers don’t necessarily produce tumors.

However, this latest research does add to the growing body of knowledge around cancer cell immune evasion and cancer immunotherapy, which is currently used as a target for many cancer therapeutics. More insight into the interaction of the immune system with cancer may help develop novel treatments for future cancers — which could involve helping immune systems remove these previously hidden cancer cells themselves.

“The state of cancer research is rapidly advancing with a strong focus on understanding the molecular mechanisms of cancer development and progression,” said Dr. Wael Harb, a hematologist and medical oncologist at MemorialCare Cancer Institute at Orange Coast Medical Center in California and vice president of medical affairs at Syneos Health.

“Studies like this contribute to our knowledge by identifying new biomarkers and potential therapeutic targets, broadening our understanding of cancer, and opening up new avenues for treatment,” Harb, who wasn’t involved in the study, told Medical News Today.

Experts say this study can potentially help more immediately in the early diagnosis of colon cancers.

“The implications for diagnosis are significant,” Harb said. “By identifying SOX17 up-regulation as a marker for early colorectal cancer, this research could lead to improved screening methods. Early detection of SOX17 could help in identifying patients at risk for more aggressive disease progression.”

Developing treatments will likely take even longer than diagnostics, but this research represents an important step in the process, experts said.

“These findings suggest new therapeutic targets,” Harb noted. “By understanding how SOX17 contributes to immune evasion, researchers can develop strategies to counteract this mechanism, potentially leading to treatments that enhance the immune system’s ability to target cancer cells.”

The researchers pointed out that because of the role of the SOX17 gene, it may be difficult to target for treatment with drugs. The next step is to try to find drugs that might interrupt mechanisms that SOX17 interacts with.

“There are many reasons that immune cells are less effective at controlling tumors,” said Dr. Daniel Landau, an oncologist and hematologist with the Mesothelioma Center at asbestos.com who was not involved in the study.

“I’ve often told patients that our immune system is most adept at destroying things that originated outside of our bodies,” Landau told Medical News Today. “The immune cells recognize antigens and when antigens are ‘foreign,’ the immune cells know to attack. Given that cancer cells originate inside the body, the immune cells don’t recognize them as foreign.”

“This is a very new discovery and confirmatory studies need to be completed, but given the evolution that cancer care has been undergoing, more ways of supporting the immune system will be needed. If a SOX 17 inhibitor could be developed, it could perhaps work similarly to the PD1/PDL1 blockers [for other cancer treatment] that are currently in widespread use,” he added.

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