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.