Page 6 - NanoString_SITC17_iBook

Expression of Programmed

Cell Death Ligand in Cutaneous

Squamous Cell Carcinoma and

Treatment of Locally Advanced

Disease With Pembrolizumab.

Stevenson ML, Wang CQ, Abikhair M, et al. Expression of Programmed Cell Death Ligand in Cutaneous
Squamous Cell Carcinoma and Treatment of Locally Advanced Disease With Pembrolizumab.
JAMA Dermatology 2017;153:299-303.

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.

https://www.ncbi.nlm.nih.gov/pubmed/28259107