TY - JOUR
T1 - Basal cell carcinoma
T2 - PD-L1/PD-1 checkpoint expression and tumor regression after PD-1 blockade
AU - Lipson, Evan J.
AU - Lilo, Mohammed T.
AU - Ogurtsova, Aleksandra
AU - Esandrio, Jessica
AU - Xu, Haiying
AU - Brothers, Patricia
AU - Schollenberger, Megan
AU - Sharfman, William H.
AU - Taube, Janis M.
N1 - Funding Information:
The authors thank Susan Markus, RN for helpful discussions. Funding This work is supported by Stand Up to Cancer (EJL, JMT), The Barney Foundation (EJL, WHS, JMT), the Dermatology Foundation (JMT), grants R01 (CA142779) (JMT) and P30 CA006973 (EJL, WHS, JMT) from the National Cancer Institute, and the Bloomberg - Kimmel Institute for Cancer Immunotherapy (EJL, WHS, JMT).
Publisher Copyright:
© 2017 The Author(s).
PY - 2017/3/21
Y1 - 2017/3/21
N2 - 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.
AB - 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.
KW - Anti-PD-1
KW - Basal cell carcinoma
KW - Hedgehog
KW - PD-L1
KW - Pembrolizumab
UR - http://www.scopus.com/inward/record.url?scp=85015666338&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85015666338&partnerID=8YFLogxK
U2 - 10.1186/s40425-017-0228-3
DO - 10.1186/s40425-017-0228-3
M3 - Article
C2 - 28344809
AN - SCOPUS:85015666338
SN - 2051-1426
VL - 5
JO - Journal for immunotherapy of cancer
JF - Journal for immunotherapy of cancer
IS - 1
M1 - 23
ER -