A recent study reveals how a groundbreaking immunotherapy helps prevent squamous cell carcinoma, with effects lasting up to five years post-treatment. This innovative therapy uniquely stimulates particular elements of the adaptive immune system, especially CD4+ T helper cells, which have not been commonly associated with traditional cancer therapies. This research opens up the possibility for the development of immunotherapies that could prevent various other types of cancer.
Clinical trial findings illustrate how the combination of topical calcipotriol and 5-fluorouracil (5-FU) activates the adaptive immune system to eradicate precancerous lesions and reduce the risk of skin cancer.
Researchers from Mass General Brigham have unveiled how a new immunotherapy approach can prevent squamous cell carcinoma, yielding benefits that persist for up to five years after treatment. This treatment is notable for being the first to engage specific aspects of the adaptive immune system, particularly focusing on CD4+ T helper cells, which are not typically engaged in standard cancer therapies. This study underscores the potential for similar immunotherapies in the prevention of other types of cancer. The findings were published in the Journal of Clinical Investigation.
Dr. Shawn Demehri, the primary author and a member of the Department of Dermatology and the Krantz Family Center for Cancer Research at Massachusetts General Hospital—part of the Mass General Brigham healthcare system—noted, “One of the significant hurdles with squamous cell carcinoma is that patients who develop it often face an elevated risk of new lesions over time. Therefore, prevention becomes a vital element of their care. We discovered that this combination of drugs prevents cancer through different mechanisms compared to existing immunotherapies, indicating that these medications might treat and prevent cancer in unique ways.”
Cancer research is a cornerstone of patient care at Mass General Brigham. By integrating research with the healthcare system’s strengths in innovation, education, and community involvement, Mass General Brigham Cancer aims to provide comprehensive cancer care with a strong emphasis on health equity. The goal is to offer a well-rounded, research-driven strategy for cancer treatment, assisting patients through every stage of their journey, from prevention and early detection to treatment and survivorship.
Squamous cell carcinoma (SCC) ranks as the second most prevalent skin cancer. Precancerous lesions, often resulting from sun exposure, indicate a higher risk of developing SCC; however, simply removing these spots does little to lower this risk. Recent findings have shown that a vitamin D derivative (calcipotriol) combined with chemotherapy (5-FU) can successfully eliminate precancerous lesions and prevent the occurrence of cancer by activating the patient’s own immune system. Nevertheless, the specific mechanism behind this effect had previously remained unclear.
Demehri’s research team conducted an open-label clinical trial to investigate how calcipotriol and 5-FU work as an immunotherapy. The study included eighteen patients with qualifying precancerous skin lesions. Participants were instructed to apply a treatment of 0.0025% calcipotriol and 2.5% 5-FU to affected areas—such as the face, scalp, and upper limbs—twice a day for six days. They underwent clinical evaluations and skin biopsies prior to treatment, one day after completing the regimen, and again eight weeks later.
The treatment effectively cleared 95% of precancerous lesions from the face, with all facial lesions eliminated in 7 out of 10 patients. The therapy led to an 82% reduction of spots on the scalp and 65% and 68% effectiveness on the right and left upper limbs, respectively. Minor side effects included some redness and inflammation around the treated areas, but all skin reactions resolved within four weeks. Importantly, surrounding healthy skin showed no adverse reactions to the drug’s immune response.
To analyze the drug’s mechanism, researchers examined skin biopsies microscopically, observing significant activity of CD4+ T cells at the sites where precancerous lesions were eliminated. They further assessed the treatment’s long-term effectiveness by continuing to collect skin biopsies from participants for five years after the trial, confirming that the effects of the immunotherapy remained significant.
To delve deeper into the drug’s mechanisms, Demehri’s lab developed a mouse model that induced tumor formation before administering the trial immunotherapy. The results showed that the treatment notably postponed tumor development and decreased tumor numbers, with these outcomes seemingly reliant on CD4+ T cell activity.
This study primarily concentrated on assessing the sustained effectiveness and actions of this immunotherapy in patients with a functioning immune system. Demehri is presently coordinating a multi-center clinical trial to determine if immunocompromised individuals, such as organ transplant recipients who are at a heightened risk for skin cancer, would experience similar benefits. Additionally, Demehri and his team are exploring how the mechanism uncovered in this trial could be adapted for use in other immunotherapies to prevent various cancers, including oral, breast, or anal cancer.
“This trial demonstrates that immunology can play a crucial role in cancer prevention, similar to how it has revolutionized cancer treatment over the past decade,” Demehri noted.
