Study on the Immune Responses Induced by ALA-Me Photodynamic Therapy

Li Anxin; Ren Jie; XiaoPubu Zhuoma

doi:10.3969/j.issn.1004-3403.2025.04.004

Abstract：Objective To investigate the antitumor immune responses induced by 5-aminolevulinic acid methyl ester hydrochloride(ALA-Me)mediated photodynamic therapy(PDT)in melanoma.Methods A non-pigmented mela-noma nude mouse model,which was challenged with human primary melanoma cells WM266-4,was established in 36 Balb/c nude mice.When the melanoma grew to a size of 0.4×0.4 cm2,the 36 nude mice were randomly divided in-to 4 groups,i.e.ALA-Me intravenous(IV)injection-PDT group,ALA-Me intraperitoneal(IP)injection-PDT group,ALA-Me external application(EA)-PDT group and a control group without any treatment.For topical application of ALA-Me,a cream with a concentration of 25 mg/cm2 was smeared on the top of tumor tissue.The tumor was irradiat-ed by an LED red light with an energy density of90 mW/cm2 and 50 J/cm2.After PDT,when the tumor growth in nude mice was significantly lower than that in the control group,the spleen cells of the nude mice were extracted and measured by flow cytometers.Results A significant increase in the number of immune natural killer(NK)cells with immunoregulatory functions was observed in the spleens of T-cell-deficient nude mice treated with ALA-Me-PDT.NK cells play a vital role in the immune system,which can recognize and eliminate virus-infected cells and tumor cells.At the same time,the number of B cells decreased,which may be correlated with the increase in NK cells,given the complex interactions and regulatory mechanisms among cells in the immune system.This finding not only reveals a novel role for ALA-Me-PDT in immune regulation,but also suggests its potential to promote the sup-pression of immune responses to melanoma.This provides important experimental data support and theoretical basis for further researches on photodynamic therapy in the field of tumor therapy,openning up new possibilities for fu-ture clinical applications.