Feasibility of Intratumoral Anti-PD1 as Treatment of Human Basal Cell Carcinoma: An Explorative Study with Adjuvant Ablative Fractional Laser
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 frac...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-11-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/23/5815 |
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| author | Silje Haukali Omland Jacob Secher Ejlertsen Dorrit Krustrup Rikke Louise Christensen Inge Marie Svane Uffe Hoegh Olesen Merete Hædersdal |
| author_facet | Silje Haukali Omland Jacob Secher Ejlertsen Dorrit Krustrup Rikke Louise Christensen Inge Marie Svane Uffe Hoegh Olesen Merete Hædersdal |
| author_sort | Silje Haukali Omland |
| collection | DOAJ |
| description | 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 (<i>p</i> = 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. |
| first_indexed | 2024-03-09T17:52:00Z |
| format | Article |
| id | doaj.art-1c3f3d2430874e52b2c42cb2754f2d89 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T17:52:00Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-1c3f3d2430874e52b2c42cb2754f2d892023-11-24T10:39:12ZengMDPI AGCancers2072-66942022-11-011423581510.3390/cancers14235815Feasibility of Intratumoral Anti-PD1 as Treatment of Human Basal Cell Carcinoma: An Explorative Study with Adjuvant Ablative Fractional LaserSilje Haukali Omland0Jacob Secher Ejlertsen1Dorrit Krustrup2Rikke Louise Christensen3Inge Marie Svane4Uffe Hoegh Olesen5Merete Hædersdal6Department of Dermatology, Copenhagen University Hospital, Bispebjerg and Frederiksberg, Copenhagen, DenmarkDepartment of Pathology, Copenhagen University Hospital, Herlev and Gentofte, Copenhagen, DenmarkDepartment of Pathology, Copenhagen University Hospital, Herlev and Gentofte, Copenhagen, DenmarkDepartment of Dermatology, Copenhagen University Hospital, Bispebjerg and Frederiksberg, Copenhagen, DenmarkDepartment of Oncology, Center for Cancer Immune Therapy, Copenhagen University Hospital, Herlev and Gentofte, Copenhagen, DenmarkDepartment of Dermatology, Copenhagen University Hospital, Bispebjerg and Frederiksberg, Copenhagen, DenmarkDepartment of Dermatology, Copenhagen University Hospital, Bispebjerg and Frederiksberg, Copenhagen, DenmarkThe 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 (<i>p</i> = 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.https://www.mdpi.com/2072-6694/14/23/5815basal cell carcinoma (BCC)keratinocyte carcinoma (KC)immune checkpoint inhibitor (ICI)anti-programmed death-1 (anti-PD1)immune responseablative fractional CO2 laser (AFL) |
| spellingShingle | Silje Haukali Omland Jacob Secher Ejlertsen Dorrit Krustrup Rikke Louise Christensen Inge Marie Svane Uffe Hoegh Olesen Merete Hædersdal Feasibility of Intratumoral Anti-PD1 as Treatment of Human Basal Cell Carcinoma: An Explorative Study with Adjuvant Ablative Fractional Laser Cancers basal cell carcinoma (BCC) keratinocyte carcinoma (KC) immune checkpoint inhibitor (ICI) anti-programmed death-1 (anti-PD1) immune response ablative fractional CO2 laser (AFL) |
| title | Feasibility of Intratumoral Anti-PD1 as Treatment of Human Basal Cell Carcinoma: An Explorative Study with Adjuvant Ablative Fractional Laser |
| title_full | Feasibility of Intratumoral Anti-PD1 as Treatment of Human Basal Cell Carcinoma: An Explorative Study with Adjuvant Ablative Fractional Laser |
| title_fullStr | Feasibility of Intratumoral Anti-PD1 as Treatment of Human Basal Cell Carcinoma: An Explorative Study with Adjuvant Ablative Fractional Laser |
| title_full_unstemmed | Feasibility of Intratumoral Anti-PD1 as Treatment of Human Basal Cell Carcinoma: An Explorative Study with Adjuvant Ablative Fractional Laser |
| title_short | Feasibility of Intratumoral Anti-PD1 as Treatment of Human Basal Cell Carcinoma: An Explorative Study with Adjuvant Ablative Fractional Laser |
| title_sort | feasibility of intratumoral anti pd1 as treatment of human basal cell carcinoma an explorative study with adjuvant ablative fractional laser |
| topic | basal cell carcinoma (BCC) keratinocyte carcinoma (KC) immune checkpoint inhibitor (ICI) anti-programmed death-1 (anti-PD1) immune response ablative fractional CO2 laser (AFL) |
| url | https://www.mdpi.com/2072-6694/14/23/5815 |
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