Immunotherapy in Nonmelanoma Skin Cancer

Soudeh Ghafouri-Fard; Somayyeh Ghafouri-Fard

Disclosures

Immunotherapy. 2012;4(5):499-510. 

In This Article

Prevention of UV-Induced Immunosuppression Is an Effective Way of Counteracting the Development of Tumors

Because of the importance of immune protection for prevention of skin cancer, different strategies intend to prevent UV-induced immunosuppression.

Anti-inflammatory Drugs

As mentioned earlier, inflammatory response of damaged skin is important in developing cancer. COX-derived prostaglandins have important roles in acute and chronic skin inflammation induced by diverse physical and chemical stimuli.[56] NSAIDs and COX-2-selective inhibitors have been shown to inhibit tumorigenesis in diverse mouse models of SCC and BCC.[56] COX-2-selective inhibitors not only suppress production of prostaglandins, but also inhibit acute inflammation signs such as proliferation of keratinocytes, and infiltration and activation of dermal neutrophils. Ultimately, inhibition of this inflammatory response may help to prevent UV-induced tumors in the skin.[57] Unselective COX inhibitor indomethacin has been shown to work against the UV-induced and PGE2–EP4-mediated systemic immunosuppression exemplified by increased Tregs in local lymph nodes.[58] Sulindac, a COX inhibitor, has been used together with the local immune modulator, 5% imiquimod, to treat SCC in situ (Bowen's disease) and it has been suggested that this combination immunotherapy may stimulate the innate, and perhaps the adaptive, immune responses.[59] COX inhibitors, in addition to acting as immune modifiers, have antiangiogenic effects.[60] The known side effects of COX inhibitors such as gastrointestinal disorders do not seem to affect their success in the reduction of skin cancer in susceptible people.

Plant Saccharides

Plant saccharides present in Aloe barbadensis have significant roles in skin protection and they specifically target pathways activated by UV radiation.[13] They can preserve the number and morphology of LCs and DCs in skin, which are the target of UV-induced immunosuppression.[61] These saccharides can preserve delayed-type hypersensitivity and cutaneous CHS suppressed by acute UV radiation. Delayed-type hypersensitivity-protective saccharides extracted from A. barbadensis prevented the systemic suppression of T-cell-mediated immune responses and the production of keratinocyte-derived IL-10 by UV-irradiated epidermal cells in both mice and humans.[11,13] In addition, fractions that prevent UV-induced suppression of CHS are shown to inhibit the production of TNF-α, which has a role in systemic suppression of immune responses.[62] Furthermore, xyloglucan extracted from the tamarind seed has been shown to prevent the production of IL-10 in UV-irradiated skin and cultured murine keratinocytes.[63]

In comparison to current strategies for photoprotection that tend to prevent UV absorption by skin, plant saccharides prevent UV-induced tissue damage. As prevention of sunburn does not necessarily lead to prevention of UV-induced immunosuppression, plant polysaccharides are superior to current sunscreens. They are also considered as additives to available sunscreen products owing to their protection against immunosuppression.[64] No possible side effect or drawback has been reported yet.

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