Blocking prostaglandin production can slow the progression of premalignant lesions into head and neck cancers — raising the possibility of using immunotherapies to treat pre-cancerous states, according to research published in Frontiers in Immunology.
The study, “Indomethacin Treatment of Mice with Premalignant Oral Lesions Sustains Cytokine Production and Slows Progression to Cancer,” showed that premalignant lesions produce high levels of prostaglandin to prevent immune cells from entering the lesions and attacking the cells before they turn into cancers.
But inhibiting prostaglandin ( a class of lipid compounds with diverse hormone-like effects) with the non-steroidal and anti-inflammatory drug indomethacin was seen in early research in mice to promote immune cell infiltration into the premalignant lesions and decreased tumor burden.
Head and neck cancers usually start with premalignant lesions in the oral cavity — the larynx, pharynx, throat, mouth, lips, salivary glands, and nasal passages. Their incidence has been decreasing over the past decades, but head and neck squamous cell carcinomas (HNSCC) — roughly 3 percent of all cancers in the United States — remain hard to treat and interventions for HNSCC, which include surgery and chemo-radiation approaches, often fail.
Researchers are trying to use immunotherapy to improve patients’ outcomes.
“There’s a lot of effort to stimulate immune reactivity using immunotherapy. The problem with that is cancer can protect itself against the immune defenses. Head and neck cancer is notorious for that,” immunologist M. Rita Young, PhD, the study’s senior author, who holds a dual appointment at the Medical University of South Carolina and the Ralph H. Johnson VA Medical Center, said in a press release.
Previous work at Young’s lab found that premalignant lesions and head and neck cancer tumors have a different immune cell composition. As premalignant lesions develop into cancer, their immune environment switched from stimulatory to immunosuppressive. The researchers now examined the role prostaglandin might have in this change.
Results showed that mice with premalignant lesions had high levels of prostaglandin, a feature that was not observed in mice already with HNSCC. Mice with the premalignant lesions were then treated with the prostaglandin inhibitor, indomethacin, to understand whether blocking prostaglandin could turn the immune environment back into an inflammatory one.
Indeed, the team found that indomethacin treatment increased the numbers of immune cells at the premalignant lesions, and led to the production of factors that activated the immune system systemically. This was associated with a reduced progression of the lesions into HNSCC.
“Immunotherapy should be considered as a treatment strategy for premalignant lesions before they progress to cancer. We can detect them. Why not treat them?” Young said.
This study suggests that administering immunotherapies to patients with premalignant lesions may boost the anti-tumor response and improve patient’s clinical outcomes. But further studies are required to understand how prostaglandin is influencing the immune system, the researchers said.
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