A new study led by researchers at Mass General Brigham reveals how a new immunotherapy prevents squamous cell carcinoma, with benefits lasting five years after treatment. This therapy is the first to activate specific components of the adaptive immune system, particularly CD4+ T helper cells, which are not known to be involved in traditional cancer treatments. This work highlights the potential for similar immunotherapies to prevent other cancers throughout the body. The results are published in the Journal of Clinical Investigation.
“One of the unique challenges of squamous cell carcinoma is that people who develop it are at increased risk of developing multiple new lesions over time. This makes prevention an essential part of care,” said corresponding author Shawn Demehri, MD, PhD, of the Department of Dermatology and the Krantz Family Center for Cancer Research at Massachusetts General Hospital, a founding member of the Mass. Health System. General Brigham. “We found that this combination of drugs prevents cancer through a mechanism distinct from those used by current immunotherapies, suggesting that these drugs may treat and prevent cancer through distinct mechanisms. »
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Squamous cell carcinoma (SCC) is the second most common type of skin cancer. Precancerous spots, often caused by sun damage, signal an increased risk of SCC, but removing individual spots does not significantly reduce the risk of developing this cancer. Recently, researchers discovered that the use of a vitamin D analogue (calcipotriol) combined with chemotherapy (5-FU) could eliminate precancerous spots and prevent the appearance of cancer by activating the patient’s immune system; However, before this trial, the mechanism remained unclear.
Demehri’s team conducted an open-label clinical trial to study the mechanism of calcipotriol and 5-FU immunotherapy. Eighteen patients with eligible precancerous skin lesions were included. Participants applied a treatment of 0.0025% calcipotriol and 2.5% 5-FU to affected areas, including the face, scalp and upper extremities, twice daily for six days. They were evaluated in the clinic and had skin biopsies taken before treatment, one day after treatment ended and again eight weeks after treatment.
The treatment successfully removed 95 percent of precancerous spots on the face and cleared all facial lesions in 7 out of 10 patients. The therapy removed 82 percent of spots on the scalp and 65 and 68 percent on the limbs. upper right and left, respectively. Side effects included redness and inflammation around the spots removed by the medication, but all skin reactions disappeared within four weeks of treatment. Notably, healthy skin did not appear to be affected by this immune response to the drug.
The researchers studied skin biopsies under a microscope to understand the mechanism of the drug and found elevated CD4+ T cell activity at sites where precancerous lesions had been removed. They assessed the drug’s long-term success by continuing to collect skin biopsies from participants more than five years after the trial, finding that the effects of immunotherapy persisted.
To better understand the drug’s mechanism, Demehri’s lab created a mouse model, inducing the development of tumors before treating the mice with the test immunotherapy. They found that the treatment significantly delayed tumor onset and reduced the number of tumors, and that these effects appeared to depend on CD4+ T cell activity.
This study focused on evaluating the long-term effectiveness and mode of action of this immunotherapy in patients with competent immune systems. Demehri is currently working on a multicenter clinical trial to evaluate whether immunocompromised people, such as organ transplant recipients at higher risk of skin cancer, would experience similar benefits. Demehri and colleagues are also exploring how the mechanism identified in this trial could be used by other immunotherapies to prevent other forms of cancer, such as oral, breast or anal cancer.
This trial demonstrates that immunology can be a powerful force in cancer prevention, just as it has transformed cancer treatment over the past decade. »
Shawn Demehri, MD, PhD, Department of Dermatology and Krantz Family Center for Cancer Research, Massachusetts General Hospital
