Feasibility of Intratumoral Anti-PD1 as Treatment of Human Basal Cell Carcinoma: An Explorative Study with Adjuvant Ablative Fractional Laser

• Published in: Cancers Vol. 14; no. 23; p. 5815
• Main Authors: Omland, Silje Haukali, Ejlertsen, Jacob Secher, Krustrup, Dorrit, Christensen, Rikke Louise, Svane, Inge Marie, Olesen, Uffe Hoegh, Hædersdal, Merete
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 25.11.2022; MDPI
• Subjects: Ablation (Vaporization technology); ablative fractional CO2 laser (AFL); anti-programmed death-1 (anti-PD1); Basal cell carcinoma; basal cell carcinoma (BCC); Biopsy; Cancer; Carcinoma; CD3 antigen; CD8 antigen; Cloning; Dermatology; Drug therapy; FDA approval; Feasibility studies; Foxp3 protein; immune checkpoint inhibitor (ICI); Immune checkpoint inhibitors; Immune response; Immunology; Immunotherapy; Infiltration; Injection; Intervention; keratinocyte carcinoma (KC); Lasers; Metastases; Metastasis; Methods; Patients; PD-1 protein; Remission; Safety; Side effects; Tumors; Denmark; United States > US; Japan; anti-programmed death-1 (anti-PD1); keratinocyte carcinoma (KC); immune response; ablative fractional CO2 laser (AFL); basal cell carcinoma (BCC); immune checkpoint inhibitor (ICI)
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers14235815

The use of immune checkpoint inhibitors (ICI) is expanding with the approval for advanced/metastatic keratinocyte carcinoma; however, most tumors are non-aggressive. Local administration could broaden ICI, but adequate immune response might require an immune-attractive adjuvant such as ablative fractional laser (AFL). Accordingly, this study aimed to explore intratumoral injection of anti-PD1 with and without AFL in basal cell carcinoma (BCC), exploring anti-PD1 concentration, immune cell infiltration, tumor response, and safety. This open-label, proof-of-concept trial investigated intratumoral anti-PD1 + AFL combination therapy versus anti-PD1 or AFL monotherapy in 28 BCC patients. The primary endpoints were immune cell infiltration evaluated immunohistochemically and clinical tumor response after 3 months. The secondary outcomes were tumoral drug concentration and safety. The most robust response was obtained following intervention with combined anti-PD1+AFL, leading to a ~2.5-fold increase in CD3+ cells ( = 0.027), and tumor reduction ≥25% in 73%, including two tumors with complete remission. Upon anti-PD1 monotherapy, a slight decrease in CD3+ cells was observed while a non-significant increase following AFL was seen. Tumor reduction ≥25% was seen in 45% and 50%, respectively, after anti-PD1 and AFL monotherapy. The CD8/CD3 ratio remained unchanged after anti-PD1+AFL and anti-PD1 monotherapy, while AFL led to a decreased ratio. A non-significant decline in the Foxp3/CD3 ratio was observed for all groups. Side-effects were mild with no systemic drug concentration detected. Intratumoral anti-PD1 injection is feasible, and a single exposure to locally injected anti-PD1 with adjuvant AFL increased immune cell infiltration and reduction in BCC with limited side-effects.