What is the expression of programmed death ligand 1 (PD-L1) in basal cell carcinomas (BCCs) given that PD-L1 expression has been associated with response to programed death 1 inhibitor immunotherapy in other tumor types?
In this cross-sectional study of 138 BCCs from 62 patients, 89.9% were positive for PD-L1 immunohistochemical staining in tumor cells, and 94.9% were positive for PD-L1 expression in tumor-infiltrating lymphocytes. In a multivariable model, PD-L1 expression of treated BCCs was significantly increased in tumor cells and tumor-infiltrating lymphocytes compared with treatment-naive BCCs.
The high rate of PD-L1 positivity in BCCs and tumor-infiltrating lymphocytes suggests that programmed death 1 inhibitor immunotherapy may have activity against BCCs.
Response to programmed death 1 (PD-1) inhibitors has been associated with programmed death ligand 1 (PD-L1) expression levels in several cancers, but PD-L1 expression and its clinical significance in basal cell carcinoma (BCC) are unknown to date.
To assess PD-L1 expression in treatment-naive and treated BCCs.
Design, Setting, and Participants
This investigation was a cross-sectional study at a single academic tertiary referral center. Immunohistochemical staining on formalin-fixed BCCs from a dermatology clinic were examined in masked fashion by a dermatopathologist and a dermatologist. The study dates were March 31, 2014, to June 7, 2016.
Treated BCCs (including those recurrent after surgery, radiotherapy, systemic chemotherapy, or topical chemotherapy) vs treatment-naive BCCs.
Main Outcomes and Measures
Percentage of tumor cells and tumor-infiltrating lymphocytes (TILs) with PD-L1 expression, intensities of expression, and association with treatment modalities.
Among 138 BCCs from 62 patients (43 males and 19 females; mean [SD] age at biopsy, 61.6 [13.7] years), 89.9% (124 of 138) were positive for PD-L1 expression in tumor cells, and 94.9% (131 of 138) were positive for PD-L1 expression in TILs, defined as greater than 5% positive immunohistochemical staining in the respective cell populations. The PD-L1 immunohistochemical staining intensity of 78 treated BCCs compared with 60 treatment-naive BCCs was significantly different in tumor cells (32% vs 7%, P = .003) and TILs (47% vs 18%, P = .008) after adjusting for the age at diagnosis. In a multivariable model adjusting for age, sex, and BCC location, PD-L1 staining intensity in tumor cells increased with the number of distinct prior treatment modalities (median, 0.12; interquartile range, 0.03-0.20; P = .007).
Conclusions and Relevance
Our data suggest that PD-1 immunotherapy may have activity against BCCs, including in those that have been previously treated. This hypothesis needs to be tested in future clinical trials.
Chang J, Zhu GA, Cheung C, Li S, Kim J, Chang ALS. Association Between Programmed Death Ligand 1 Expression in Patients With Basal Cell Carcinomas and the Number of Treatment Modalities. JAMA Dermatol. Published online March 04, 2017. doi:10.1001/jamadermatol.2016.5062