Enhanced Systemic Immune Reactivity to a Basal Cell Carcinoma Associated Antigen Following Photodynamic Therapy

• Published in: Clinical cancer research 2009-07, Vol.15 (13), p.4460-4466
• Main Authors: KABINGU, Edith, OSEROFF, Allan R, WILDING, Gregory E, GOLLNICK, Sandra O
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Amino Acid Sequence; anti-tumor immunity; Antigens, Neoplasm - immunology; Antineoplastic agents; basal cell carcinoma; Biological and medical sciences; Carcinoma, Basal Cell - drug therapy; Carcinoma, Basal Cell - immunology; Child; Dermatology; DNA-Binding Proteins - chemistry; DNA-Binding Proteins - immunology; DNA-Binding Proteins - metabolism; Epitope Mapping; Female; HLA-A2 Antigen - metabolism; Humans; Immunity, Cellular - physiology; Male; Medical sciences; Middle Aged; Peptide Fragments - analysis; Peptide Fragments - immunology; Peptide Fragments - metabolism; Pharmacology. Drug treatments; Photochemotherapy; photodynamic therapy; Protein Binding - immunology; Skin Neoplasms - drug therapy; Skin Neoplasms - immunology; Tumors of the skin and soft tissue. Premalignant lesions; Up-Regulation - immunology; Young Adult
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-09-0400

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 PDT of 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 PDT or 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 Hip1 peptide was measured by INF-γ ELISpot assay. Results: Immune recognition of Hip1 increased 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 compared with patients with nodular lesions. Immune reactivity following PDT was inversely correlated with treatment area and light dose. Conclusions: These findings show for the first time that local tumor PDT can enhance systemic immune responses to tumors in patients, and validate previous preclinical findings.