Enhanced systemic immune reactivity to a basal cell carcinoma associated antigen following photodynamic therapy

Purpose: Numerous preclinical studies have shown that local photodynamic therapy (PDT) of tumors enhances systemic antitumor immunity. However, other than single-case and anecdotal reports, this phenomenon has not been examined following clinical PDT. To determine whether PDT in a clinical setting enhances systemic recognition of tumor cells, we examined whether PDTof basal cell carcinoma resulted in an increased systemic immune response to Hip1, a tumor antigen associated with basal cell carcinoma. Experimental Design: Basal cell carcinoma lesions were either treated with PDTor surgically removed. Blood was collected from patients immediately before or 7 to 10 days following treatment. Peripheral blood leukocytes were isolated from HLA-A2 - expressing patients and reactivity to a HLA-A2- restricted Hip1peptide was measured by INF-g ELISpot assay. Results: Immune recognition of Hip1increased in patients whose basal cell carcinoma lesions were treated with PDT. This increase in reactivity was significantly greater than reactivity observed in patients whose lesions were surgically removed. Patients with superficial lesions exhibited greater enhancement of reactivity comparedwith patientswith nodular lesions. Immune reactivity following PDTwas inversely correlated with treatment area and light dose. Conclusions:These findings show for the first time that local tumor PDTcan enhance systemic immune responses to tumors in patients, and validate previous preclinical findings.