Basal cell carcinoma: PD-L1/PD-1 checkpoint expression and tumor regression after PD-1 blockade
Monoclonal antibodies that block immune regulatory proteins such as programmed death-1 (PD-1) have demonstrated remarkable efficacy in controlling the growth of multiple tumor types. Unresectable or metastatic basal cell carcinoma, however, has largely gone untested. Because PD-Ligand-1 (PD-L1) expr...
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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2017-08-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/5/1/23.full |
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| author | Megan Schollenberger Evan Lipson William H. Sharfman Janis M. Taube Haiying Xu Aleksandra Ogurtsova Jessica Esandrio Mohammed T. Lilo Patricia Brothers |
| author_facet | Megan Schollenberger Evan Lipson William H. Sharfman Janis M. Taube Haiying Xu Aleksandra Ogurtsova Jessica Esandrio Mohammed T. Lilo Patricia Brothers |
| author_sort | Megan Schollenberger |
| collection | DOAJ |
| description | Monoclonal antibodies that block immune regulatory proteins such as programmed death-1 (PD-1) have demonstrated remarkable efficacy in controlling the growth of multiple tumor types. Unresectable or metastatic basal cell carcinoma, however, has largely gone untested. Because PD-Ligand-1 (PD-L1) expression in other tumor types has been associated with response to anti-PD-1, we investigated the expression of PD-L1 and its association with PD-1 expression in the basal cell carcinoma tumor microenvironment. Among 40 basal cell carcinoma specimens, 9/40 (22%) demonstrated PD-L1 expression on tumor cells, and 33/40 (82%) demonstrated PD-L1 expression on tumor-infiltrating lymphocytes and associated macrophages. PD-L1 was observed in close geographic association to PD-1+ tumor infiltrating lymphocytes. Additionally, we present, here, the first report of an objective anti-tumor response to pembrolizumab (anti-PD-1) in a patient with metastatic PD-L1 (+) basal cell carcinoma, whose disease had previously progressed through hedgehog pathway-directed therapy. The patient remains in a partial response 14 months after initiation of therapy. Taken together, our findings provide a rationale for testing anti-PD-1 therapy in patients with advanced basal cell carcinoma, either as initial treatment or after acquired resistance to hedgehog pathway inhibition. |
| format | Article |
| id | doaj-art-be0f8a78611d45c494dace76b4e64c27 |
| institution | OA Journals |
| issn | 2051-1426 |
| language | English |
| publishDate | 2017-08-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-be0f8a78611d45c494dace76b4e64c272025-08-20T02:12:49ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262017-08-015110.1186/s40425-017-0228-3Basal cell carcinoma: PD-L1/PD-1 checkpoint expression and tumor regression after PD-1 blockadeMegan Schollenberger0Evan Lipson1William H. Sharfman2Janis M. Taube3Haiying Xu4Aleksandra Ogurtsova5Jessica Esandrio6Mohammed T. Lilo7Patricia Brothers8Aff1 0000 0001 2171 9311grid.21107.35Department of OncologyJohns Hopkins University School of Medicine, Sidney Kimmel Comprehensive Cancer Center, and Bloomberg ~ Kimmel Institute for Cancer Immunotherapy Baltimore MD USA1 Johns Hopkins Bloomberg~Kimmel Institute for Cancer Immunotherapy, Baltimore, Maryland, USAAff1 0000 0001 2171 9311grid.21107.35Department of OncologyJohns Hopkins University School of Medicine, Sidney Kimmel Comprehensive Cancer Center, and Bloomberg ~ Kimmel Institute for Cancer Immunotherapy Baltimore MD USAAff1 0000 0001 2171 9311grid.21107.35Department of OncologyJohns Hopkins University School of Medicine, Sidney Kimmel Comprehensive Cancer Center, and Bloomberg ~ Kimmel Institute for Cancer Immunotherapy Baltimore MD USA1 Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA1Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, MD, USAAff2 0000 0001 2171 9311grid.21107.35Department of PathologyJohns Hopkins University School of Medicine, Sidney Kimmel Comprehensive Cancer Center, and Bloomberg ~ Kimmel Institute for Cancer Immunotherapy Baltimore MD USAAff2 0000 0001 2171 9311grid.21107.35Department of PathologyJohns Hopkins University School of Medicine, Sidney Kimmel Comprehensive Cancer Center, and Bloomberg ~ Kimmel Institute for Cancer Immunotherapy Baltimore MD USAAff1 0000 0001 2171 9311grid.21107.35Department of OncologyJohns Hopkins University School of Medicine, Sidney Kimmel Comprehensive Cancer Center, and Bloomberg ~ Kimmel Institute for Cancer Immunotherapy Baltimore MD USAMonoclonal antibodies that block immune regulatory proteins such as programmed death-1 (PD-1) have demonstrated remarkable efficacy in controlling the growth of multiple tumor types. Unresectable or metastatic basal cell carcinoma, however, has largely gone untested. Because PD-Ligand-1 (PD-L1) expression in other tumor types has been associated with response to anti-PD-1, we investigated the expression of PD-L1 and its association with PD-1 expression in the basal cell carcinoma tumor microenvironment. Among 40 basal cell carcinoma specimens, 9/40 (22%) demonstrated PD-L1 expression on tumor cells, and 33/40 (82%) demonstrated PD-L1 expression on tumor-infiltrating lymphocytes and associated macrophages. PD-L1 was observed in close geographic association to PD-1+ tumor infiltrating lymphocytes. Additionally, we present, here, the first report of an objective anti-tumor response to pembrolizumab (anti-PD-1) in a patient with metastatic PD-L1 (+) basal cell carcinoma, whose disease had previously progressed through hedgehog pathway-directed therapy. The patient remains in a partial response 14 months after initiation of therapy. Taken together, our findings provide a rationale for testing anti-PD-1 therapy in patients with advanced basal cell carcinoma, either as initial treatment or after acquired resistance to hedgehog pathway inhibition.https://jitc.bmj.com/content/5/1/23.full |
| spellingShingle | Megan Schollenberger Evan Lipson William H. Sharfman Janis M. Taube Haiying Xu Aleksandra Ogurtsova Jessica Esandrio Mohammed T. Lilo Patricia Brothers Basal cell carcinoma: PD-L1/PD-1 checkpoint expression and tumor regression after PD-1 blockade Journal for ImmunoTherapy of Cancer |
| title | Basal cell carcinoma: PD-L1/PD-1 checkpoint expression and tumor regression after PD-1 blockade |
| title_full | Basal cell carcinoma: PD-L1/PD-1 checkpoint expression and tumor regression after PD-1 blockade |
| title_fullStr | Basal cell carcinoma: PD-L1/PD-1 checkpoint expression and tumor regression after PD-1 blockade |
| title_full_unstemmed | Basal cell carcinoma: PD-L1/PD-1 checkpoint expression and tumor regression after PD-1 blockade |
| title_short | Basal cell carcinoma: PD-L1/PD-1 checkpoint expression and tumor regression after PD-1 blockade |
| title_sort | basal cell carcinoma pd l1 pd 1 checkpoint expression and tumor regression after pd 1 blockade |
| url | https://jitc.bmj.com/content/5/1/23.full |
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