Pancreatic cancer is difficult to detect and treat because tumors can develop quietly and remaining cancer cells often cause recurrence after surgery. Darren Carpizo of the Wilmot Cancer Institute led a University of Rochester Medicine study published in Developmental Cell that examined how pancreatic tumor cells evade immune attack and how this knowledge might improve immunotherapy.
The team discovered that the gene Dec2 helps pancreatic cancer cells hide from killer T cells by regulating a molecule on the tumor cell surface. Laboratory experiments showed that knocking out Dec2 allowed immune cells to recognise and destroy the cancer cells. Dec2 also follows a circadian rhythm: its levels rise and fall during the day, and the time of day influenced how effectively T cells killed pancreatic cancer cells. This may help explain why clinicians sometimes see better immunotherapy responses in the morning than in the evening.
The study could shed light on mixed results from a small Memorial Sloan Kettering mRNA vaccine trial: of 16 patients, eight who generated an immune response remained alive for several years, while eight did not respond. Carpizo and colleagues developed a mouse model that mirrors human pancreatic cancer and its protective microenvironment to test these ideas. The research was supported by a pilot grant from Wilmot and by the National Cancer Institute. Possible next steps are testing Dec2-targeting approaches or timing treatments by circadian rhythm, but it is not yet clear how soon these strategies could enter clinical trials.
Difficult words
- evade — avoid being detected or attacked
- recurrence — return of disease after earlier treatment
- immunotherapy — treatment that uses the immune system
- circadian rhythm — natural daily cycle of biological activity
- microenvironment — local cells and molecules around a tumor
- knock out — to disable a gene or protein functionknocking out
Tip: hover, focus or tap highlighted words in the article to see quick definitions while you read or listen.
Discussion questions
- How might timing cancer treatment by circadian rhythm improve patient outcomes? Explain with reasons from the article.
- What are potential benefits and risks of developing treatments that target a gene like Dec2 to help the immune system attack tumors?
- Why is a mouse model that mirrors human pancreatic cancer and its protective microenvironment important for testing new ideas?
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