Anti-melanoma Effects of Resiquimod (RSQ) In Vitro and in Combination with Immune Checkpoint Blockade In Vivo

Melanoma is the deadliest form of skin cancer and surgery is currently the most effective treatment. However, there are situations where surgery fails or is not an option to treat melanoma patients. Immunotherapy such as immune checkpoint blockade (e.g., anti-PD-1) can be effective as an alternative...

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Published in:	The AAPS journal 2023-06, Vol.25 (4), p.57-57, Article 57
Main Authors:	Tambunlertchai, Supreeda, Geary, Sean M., Naguib, Youssef W., Salem, Aliasger K.
Format:	Article
Language:	eng
Subjects:	Animals Biochemistry Biomedical and Life Sciences Biomedicine Biotechnology Cancer Care and treatment Immune Checkpoint Inhibitors - pharmacology Immune Checkpoint Inhibitors - therapeutic use Immunotherapy Immunotherapy - methods Melanoma Melanoma - drug therapy Melanoma - pathology Mice Pharmacology/Toxicology Pharmacy Recent Advances in Drug Delivery Research Article Skin cancer Skin Neoplasms - drug therapy Tumor Microenvironment
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Summary:	Melanoma is the deadliest form of skin cancer and surgery is currently the most effective treatment. However, there are situations where surgery fails or is not an option to treat melanoma patients. Immunotherapy such as immune checkpoint blockade (e.g., anti-PD-1) can be effective as an alternative treatment for melanoma patients; however, the percentage of melanoma patients that exhibit complete responses from anti-PD-1 monotherapy is low, and a hostile immunosuppressive tumor microenvironment may be at least partly responsible. Resiquimod (RSQ) is an imidazoquinolinamine derivative and TLR-7/8 agonist that could enhance the antitumor activity of immune checkpoint blockade when these agents are combined as a treatment for melanoma. Here, the effect of combining systemic anti-PD-1 and locally administered RSQ on the survival of melanoma-challenged mice was tested. Our results demonstrated that anti-PD-1 in combination with RSQ can significantly prolong the survival of melanoma-challenged mice, compared to untreated mice and mice treated with anti-PD-1 alone. In addition, the in vitro studies showed that RSQ can mediate a direct anti-proliferative effect on melanoma cells. In conclusion, the combination of RSQ and anti-PD-1 may be a promising treatment for melanoma patients, especially as both treatments have already been used independently to safely treat melanoma patients. Graphical Abstract
ISSN:	1550-7416 1550-7416