title: Expression of Programmed Cell Death Ligand in Cutaneous Squamous Cell Carcinoma and Treatment of Locally Advanced Disease With Pembrolizumab.
abstract: OBJECTIVE
  Limited therapies are available in patients with inoperable locally advanced cutaneous squamous cell carcinoma (cSCC).
  
  
  OBJECTIVE
  To determine the efficacy of programmed cell death 1 receptor (PD-1) inhibitors in locally advanced cSCC.
  
  
  METHODS
  A single patient with locally advanced cSCC who declined surgery and radiotherapy underwent treatment with pembrolizumab, an anti-PD-1 antibody, at an academic dermatologic surgery section and cancer center. The patient was followed up for clinical and radiologic regression of cSCC. With the use of NanoString to amplify potential biomarkers, immunohistochemistry, and immunofluorescence, the ex vivo expression of PD-1 and a ligand (PD-L2) was assessed in 38 cSCC biopsy specimens from 24 patients with cSCC. Expression of PD-L1 and PD-L2 in the cSCC microenvironment was defined.
  
  
  METHODS
  Pembrolizumab, 2 mg/kg every 3 weeks, for 4 cycles.
  
  
  METHODS
  Expression of PD-L1 and PD-L2 in the cSCC microenvironment.
  
  
  RESULTS
  In 1 patient with locally advanced cSCC who was treated with pembrolizumab, nearly complete tumor regression was observed after 4 cycles of therapy. The NanoString technology used in 38 cSCC biopsy specimens from 24 patients with cSCC (19 men and 5 women; mean [SD] age, 76.4 [12.2] years) detected increased PD-1 and PD-L2 expression in high-risk cSCC. Immunohistochemical analysis confirmed enhanced expression of PD-1 and its ligands in cSCC with perineural invasion (mean [SEM] expression, 5.06 [1.27]; P = .05), superficial cSCC (mean [SEM] expression, 3.58 [1.50]; P = .15), organ transplant-associated cSCC (mean [SEM] expression, 3.01 [0.54]; P = .005), and infiltrative cSCC (mean [SD] expression, 2.01 [0.30]; P = .006) compared with normal skin specimens. In double-label immunofluorescence staining, CD11c+, a marker of myeloid dendritic cells, colocalized with PD-L1 and PD-L2 in cSCC lesions.
  
  
  CONCLUSIONS
  The favorable treatment response combined with significant involvement of PD-1 and PD ligands in cSCC lesions suggests that PD-1 blockade may be a viable therapeutic option for locally advanced cSCC and provides rationale for further investigation in future clinical trials.
authors.affiliation: Ronald O. Perelman Department of Dermatology, New York University Langone Medical Center, New York, New York.
authors.forename: Mary L
authors.initials: ML
authors.lastname: Stevenson
authors.affiliation: Laboratory for Investigative Dermatology, Rockefeller University, New York, New York.
authors.forename: Claire Q F
authors.initials: CQ
authors.lastname: Wang
authors.affiliation: Ronald O. Perelman Department of Dermatology, New York University Langone Medical Center, New York, New York.
authors.forename: Melody
authors.initials: M
authors.lastname: Abikhair
authors.affiliation: Ronald O. Perelman Department of Dermatology, New York University Langone Medical Center, New York, New York.
authors.forename: Nazanin
authors.initials: N
authors.lastname: Roudiani
authors.affiliation: Institute for Pediatric Urology, Weill Cornell Medicine, Cornell University, New York, New York.
authors.forename: Diane
authors.initials: D
authors.lastname: Felsen
authors.affiliation: Laboratory for Investigative Dermatology, Rockefeller University, New York, New York.
authors.forename: James G
authors.initials: JG
authors.lastname: Krueger
authors.affiliation: Laura and Isaac Perlmutter Cancer Center, New York University Langone Medical Center, New York, New York.
authors.forename: Anna C
authors.initials: AC
authors.lastname: Pavlick
authors.affiliation: Ronald O. Perelman Department of Dermatology, New York University Langone Medical Center, New York, New York.
authors.forename: John A
authors.initials: JA
authors.lastname: Carucci
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D060890:B7-H1 Antigen / Q000378:metabolism; D001706:Biopsy; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D061027:Programmed Cell Death 1 Ligand 2 Protein / Q000378:metabolism; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors*; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome; D059016:Tumor Microenvironment
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D060890:B7-H1 Antigen; C556977:PDCD1LG2 protein, human; D061027:Programmed Cell Death 1 Ligand 2 Protein; D061026:Programmed Cell Death 1 Receptor; C582435:pembrolizumab