title: Basal cell carcinoma: PD-L1/PD-1 checkpoint expression and tumor regression after PD-1 blockade.
abstract: 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.
authors.affiliation: Department of Oncology, Johns Hopkins University School of Medicine, Sidney Kimmel Comprehensive Cancer Center, and Bloomberg ~ Kimmel Institute for Cancer Immunotherapy, Baltimore, MD USA.|Melanoma and Cancer Immunology Programs, Johns Hopkins University School of Medicine, 1550 Orleans Street, Room 507, Baltimore, MD 21231 USA.
authors.forename: Evan J
authors.initials: EJ
authors.lastname: Lipson
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Sidney Kimmel Comprehensive Cancer Center, and Bloomberg ~ Kimmel Institute for Cancer Immunotherapy, Baltimore, MD USA.
authors.forename: Mohammed T
authors.initials: MT
authors.lastname: Lilo
authors.affiliation: Department of Dermatology, Johns Hopkins University School of Medicine, Sidney Kimmel Comprehensive Cancer Center, and Bloomberg ~ Kimmel Institute for Cancer Immunotherapy, Baltimore, MD USA.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Ogurtsova
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Sidney Kimmel Comprehensive Cancer Center, and Bloomberg ~ Kimmel Institute for Cancer Immunotherapy, Baltimore, MD USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Esandrio
authors.affiliation: Department of Dermatology, Johns Hopkins University School of Medicine, Sidney Kimmel Comprehensive Cancer Center, and Bloomberg ~ Kimmel Institute for Cancer Immunotherapy, Baltimore, MD USA.
authors.forename: Haiying
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Oncology, Johns Hopkins University School of Medicine, Sidney Kimmel Comprehensive Cancer Center, and Bloomberg ~ Kimmel Institute for Cancer Immunotherapy, Baltimore, MD USA.
authors.forename: Patricia
authors.initials: P
authors.lastname: Brothers
authors.affiliation: Department of Oncology, Johns Hopkins University School of Medicine, Sidney Kimmel Comprehensive Cancer Center, and Bloomberg ~ Kimmel Institute for Cancer Immunotherapy, Baltimore, MD USA.
authors.forename: Megan
authors.initials: M
authors.lastname: Schollenberger
authors.affiliation: Department of Oncology, Johns Hopkins University School of Medicine, Sidney Kimmel Comprehensive Cancer Center, and Bloomberg ~ Kimmel Institute for Cancer Immunotherapy, Baltimore, MD USA.
authors.forename: William H
authors.initials: WH
authors.lastname: Sharfman
authors.affiliation: Department of Oncology, Johns Hopkins University School of Medicine, Sidney Kimmel Comprehensive Cancer Center, and Bloomberg ~ Kimmel Institute for Cancer Immunotherapy, Baltimore, MD USA.|Department of Pathology, Johns Hopkins University School of Medicine, Sidney Kimmel Comprehensive Cancer Center, and Bloomberg ~ Kimmel Institute for Cancer Immunotherapy, Baltimore, MD USA.|Department of Dermatology, Johns Hopkins University School of Medicine, Sidney Kimmel Comprehensive Cancer Center, and Bloomberg ~ Kimmel Institute for Cancer Immunotherapy, Baltimore, MD USA.
authors.forename: Janis M
authors.initials: JM
authors.lastname: Taube
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000009:adverse effects; D060890:B7-H1 Antigen / Q000037:antagonists & inhibitors / Q000276:immunology*; D002280:Basal Cell Carcinoma / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D053823:Hedgehog Proteins / Q000037:antagonists & inhibitors / Q000235:genetics; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects; D059016:Tumor Microenvironment / Q000187:drug effects / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D060890:B7-H1 Antigen; C423236:CD274 protein, human; D053823:Hedgehog Proteins; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; C582435:pembrolizumab
keywords: Anti-PD-1; Basal cell carcinoma; Hedgehog; PD-L1; Pembrolizumab