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Brief Report
March 4, 2017

Expression of Programmed Cell Death Ligand in Cutaneous Squamous Cell Carcinoma and Treatment of Locally Advanced Disease With Pembrolizumab

Author Affiliations
  • 1Ronald O. Perelman Department of Dermatology, New York University Langone Medical Center, New York, New York
  • 2Laboratory for Investigative Dermatology, Rockefeller University, New York, New York
  • 3Institute for Pediatric Urology, Weill Cornell Medicine, Cornell University, New York, New York
  • 4Laura and Isaac Perlmutter Cancer Center, New York University Langone Medical Center, New York, New York
JAMA Dermatol. Published online March 4, 2017. doi:10.1001/jamadermatol.2016.5118
Key Points

Question  Can programmed cell death 1 protein inhibitors effectively treat cutaneous squamous cell carcinoma?

Findings  In a patient with locally advanced cutaneous squamous cell carcinima, nearly complete tumor regression was observed after 4 cycles of therapy with pembrolizumab; after 11 months of maintenance therapy, the immunocompetent patient had no clinical evidence of disease. In 38 biopsy specimens from 24 patients with high-risk cutaneous squamous cell carcinoma, expression of programmed cell death 1 and ligand 2 was increased.

Meaning  The favorable treatment response combined with significant involvement of programmed cell death 1 and its ligands in cutaneous squamous cell carcinoma lesions suggest that blockade may be a viable therapeutic option for locally advanced disease.

Abstract

Importance  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.

Design, Setting, and Participants  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.

Intervention  Pembrolizumab, 2 mg/kg every 3 weeks, for 4 cycles.

Main Outcomes and Measures  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 and Relevance  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.

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