Light-Based Immunotherapy for Skin Cancer

In previous Discoveries posts, we explored the synergy between photodynamic therapy (PDT) and strategies that enhance the immune system. PDT has the marvelous ability to not only destroy tumors in a targeted manner, but also to improve the immune system’s ability to recognize and remove cancer cells. When combined with immunotherapy, the ability to eradicate cancer can be greatly increased.

The common skin cancer called basal cell carcinoma (BCC) offers a nice example of the power of a light-based immunotherapy approach. Excessive exposure to ultraviolet radiation from the sun is considered to be a major cause of BCC. It is known that this form of radiation not only causes mutations but also results in various immune system imbalances in the skin. These immune changes basically show up as an increased level of certain T regulatory cells along with lower levels of effector T cells. Such changes ultimately lead to a suppressed immune system within the skin, making it easier for skin cancer to develop.

In conventional medicine, surgery is viewed as the first treatment of choice for BCC, while radiotherapy and topical chemotherapy (5-FU) are favored for inoperable tumors. But surgery can leave an unsightly scar in some cases, while chemo and radiation treatments often have toxic side effects.   Moreover, the diagnosis of BCC is frequently carried out on patients with multiple health problems or “comorbidities”, and this has forced doctors to search for alternative, minimally invasive, and less toxic treatments.

PDT is the logical “go to” option for many of these cases. The photosensitizing agent is administered as a cream on the lesion, and this is followed by treatment with light of a specific wavelength. The resulting photodynamic reaction causes the release of reactive oxygen molecules that destroy the cancer cells. The only real side effect is that some patients will experience some pain during the light treatment.


A More Complete Light-Based Treatment

Today PDT, using the photosensitizer called methylaminolevulinate, is widely regarded as an effective treatment for superficial and small nodular BCC. These skin cancers rarely pose a threat to life, as metastasis is extremely rare. On the other hand, the tumor is locally invasive and can infiltrate and destroy the tissue below the skin, including, bone and cartilage, eventually even reaching vital structures such as major vessels or nervous system.

For these reasons, and in order to further lower the risk of a recurrence, doctors have begun combining PDT with immunotherapy. The best studied immunotherapy strategy is a drug called imiquimod (brand name Aldara). This prescription medication is applied as a cream and acts as an immune response modifier for the treatment of superficial BCC as well as actinic keratosis and genital warts.

Imiquimod works by increasing the release of pro-inflammatory chemicals (cytokines), which in turn can trigger the production of certain immune cells that attack the cancer. It is currently approved for the treatment of small superficial BCC. When combined with PDT, however, imiquimod also becomes effective against more aggressive, recurrent forms of BCC that tend to resist the effects of radiotherapy and chemotherapy.

In a 2012 randomized clinical trial of recurrent BCC, PDT combined with a placebo cream was compared to PDT with topical applications of imiquimod.   A complete remission was seen in 60% of the patients from the first group, compared to 75% in the second group. Thus, the light-based immunotherapy strategy produced a superior result.

In very large or “giant BCC” lesions, this same light-based immunotherapy strategy results in a dramatic shrinking of the tumor. This, in turn, allows for safe and effective surgery to eliminate the remaining malignant tissue, as reported in the 28 October 2015 International Journal of Molecular Science.

This example raises an important point about the use of the PDT-imiquimod combination strategy: It can help set the stage for more effective surgery if the tumor is too large, or if the patient’s condition is too delicate for undergoing more aggressive surgery. Reducing the need for surgery, chemotherapy and radiotherapy could ultimately give way to a more humane and effective way of treating cancer—what we refer to as the photoimmune way.

One last important note about the light-based immunotherapy approach is that no significant differences in BCC recurrence rates have been found when patients with intact immune systems were compared to those with severely compromised immune systems (organ transplant patients). This shows the feasibility of the PDT-imiquimod method in patients for whom conventional treatment methods.

Along similar lines, excellent results were reported in two children with bone marrow tansplant who were suffering from the a potentially precancerous skin disorder called Porokeratosis. This condition can sometimes lead to squamous cell carcinoma of the skin. The photoimmune treatment once again involved PDT with imiquimod, as reported in the November 2015 issue of Pediatric Dermatology.



Lucena SR, Salazar N, Gracia-Cazaña T, Zamarrón A, González S, Juarranz Á, Gilaberte Y. Combined Treatments with Photodynamic Therapy for Non-Melanoma Skin Cancer. Int J Mol Sci. 2015 Oct 28;16(10):25912-33.

Roozeboom MH, van Kleef L, Arits AH, Mosterd K, Winnepenninckx VJ, van Marion AM, Nelemans PJ, Kelleners-Smeets NW. Tumor thickness and adnexal extension of superficial basal cell carcinoma (sBCC) as determinants of treatment failure for methylaminolevulinate (MAL)-photodynamic therapy (PDT), imiquimod, and 5-fluorouracil (FU). J Am Acad Dermatol. 2015 Jul;73(1):93-8.

Papakostas D, Stockfleth E. Topical treatment of basal cell carcinoma with the immune response modifier imiquimod. Future Oncol. 2015 Nov;11(22):2985-90.

Osiecka B, Jurczyszyn K, Ziolkowski P. The application of Levulan-based photodynamic therapy with imiquimod in the treatment of recurrent basal cell carcinoma. Med. Sci. Monit. 2012, 18, 15–18.

Gracia-Cazaña T, Vera-Álvarez J, García-Patos V, Gilaberte Y. Imiquimod and Photodynamic Therapy Are Useful in the Treatment of Porokeratosis in Children with Bone Marrow Transplantation. Pediatr Dermatol. 2015 Nov;32(6):e291-3.