Maintaining immune cells in head and neck cancer

 By Matthew Greseth

Researchers at the Medical University of South Carolina and the Ralph H. Johnson VA Medical Center are trying to improve the treatment of head and neck cancers by enhancing the body’s immune system to attack the tumors. 

In an article published in Frontiers in Immunology, they report that inhibiting prostaglandin production slows the progression of premalignant areas to become head and neck squamous cell carcinoma (HNSCC). Prostaglandins are lipid compounds that regulate inflammation.

Preclinical studies showed that treatment of premalignant lesions with indomethacin, a nonsteroidal anti-inflammatory drug similar to aspirin, increased the presence of immune cells and lessened tumor burden. 

Cancers of the head and neck begin with lesions in the oral cavity, including the larynx, pharynx, throat, lips, mouth, salivary glands and nasal passages. Although the incidence of HNSCC has been on the decline over the past several decades, the National Cancer Institute reports that approximately 3 percent of all cancers in the U.S. result from HNSCC, with men being diagnosed twice as often as women. Treatment includes surgical removal and chemo-radiation treatment. However, these interventions often fail, and patients have a five-year survival rate of only 50 percent. 

Immunologist M. Rita Young, Ph.D., senior author for this study, holds a dual appointment at MUSC and the Ralph H. Johnson VA Medical Center. She said 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.”

She’s been working on addressing the problem by studying how the immune system affects tumor progression. Previous work from her laboratory has shown the composition of immune cells within premalignant lesions differs from those within HNSCC. 

Significantly, as premalignant cells develop into HNSCC, the immune environment switches from stimulatory and inflammatory to immunosuppressive. This keeps the immune system from combating the cancer. Prostaglandin may be an important mediator of this switch.

Young’s study used a novel mouse model of HNSCC to determine how inhibition of prostaglandin affects tumor progression. She found that indomethacin, an NSAID that inhibits the production of prostaglandin, increased the presence of immune cells at the lesion site and led to a systemic activation of the immune system. 

Future studies in this area will be focused on maintaining a strong immune presence in premalignant lesions for patients. If studies in humans bear out these preclinical findings, further research using more specific prostaglandin inhibitors in combination with other immunomodulatory compounds could provide a better treatment regimen to prevent the formation of 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?” said Young. Also, these intervention strategies may be able to help prevent smaller, as yet undetectable lesions from progressing to HNSCC.

Matthew Greseth, Ph.D., is a postdoctoral fellow in the Traktman Laboratory in the Department of Microbiology and Immunology at MUSC.