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- Title
Feasibility of Intratumoral Anti-PD1 as Treatment of Human Basal Cell Carcinoma: An Explorative Study with Adjuvant Ablative Fractional Laser.
- Authors
Omland, Silje Haukali; Ejlertsen, Jacob Secher; Krustrup, Dorrit; Christensen, Rikke Louise; Svane, Inge Marie; Olesen, Uffe Hoegh; Hædersdal, Merete
- Abstract
Simple Summary: The use of immune checkpoint inhibitors (ICI) is expanding with the approval for locally advanced and metastasizing keratinocyte carcinoma. Most cases, however, are non-aggressive. Systemic therapy remains limited by severe side effects. Local administration could broaden ICI, but an adequate immune response might require an immune-attractive adjuvant such as ablative fractional laser (AFL). Accordingly, aiming to broaden the field of ICI to keratinocyte carcinoma, this study investigates the 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. With the results of the study showing the feasibility of intratumoral anti-PD1 and increase in immune cell infiltration and tumor reduction upon combined anti-PD1 and AFL, local, hence broader, application of anti-PD1 holds potential for future treatment of non-aggressive keratinocyte carcinomas. 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 (p = 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.
- Subjects
DENMARK; ADJUVANT chemotherapy; DRUG efficacy; RESEARCH; IMMUNE checkpoint inhibitors; INJECTIONS; CLINICAL trials; IMMUNOHISTOCHEMISTRY; LASER therapy; CANCER patients; DESCRIPTIVE statistics; BASAL cell carcinoma; EVALUATION
- Publication
Cancers, 2022, Vol 14, Issue 23, p5815
- ISSN
2072-6694
- Publication type
Article
- DOI
10.3390/cancers14235815