TY - JOUR
T1 - A Distinct Pretreatment Immune Gene Signature in Lentigo Maligna Is Associated with Imiquimod Response
AU - Halse, Heloise
AU - Caramia, Franco
AU - McLean, Catriona A.
AU - Wang, Minyu
AU - Aw Yeang, Han Xian
AU - Keam, Simon P.
AU - Behren, Andreas
AU - Ly, Lena
AU - Haskett, Martin
AU - Cebon, Jonathan
AU - McArthur, Grant A.
AU - Neeson, Paul J.
AU - Mar, Victoria J.
N1 - Funding Information:
PJN has received research project funding from BMS, Roche Genentech, Allergan, Juno/Celgene, and Compugen. PJN has received honorarium from BMS. VJM has received a National Health and Medical Research Council Early Career Fellowship and a Victorian Cancer Agency translation research grant. VJM has received honoraria from Merck and Bristol-Myers-Squibb not related to this manuscript. The other authors have no conflict of interest to declare.
Funding Information:
This project was supported by funding from the Victorian Cancer Agency, Melbourne Melanoma Project (now Melanoma Research Victoria). Andreas Behren is supported by a fellowship from the Department of Health and Human Services acting through the Victorian Cancer Agency. The authors wish to acknowledge Gisela Mir Arnau and Tim Holloway (Molecular Genomics Core Facility, Peter MacCallum Cancer Centre) for provision of the NanoString nCounter Analysis System for gene expression profiling. The authors wish to acknowledge the work of pathologists Rod O'Keefe, John P. Dowling, and Sara Swain who reported patient outcomes in the original trial. We thank Tim Holloway and Gisela Mir Anau (Genomics Facility, Peter MacCallum Cancer Center) for their technical support, and Sonia Mailer (Melanoma Research Victoria) for her assistance.
Funding Information:
This project was supported by funding from the Victorian Cancer Agency , Melbourne Melanoma Project (now Melanoma Research Victoria). Andreas Behren is supported by a fellowship from the Department of Health and Human Services acting through the Victorian Cancer Agency . The authors wish to acknowledge Gisela Mir Arnau and Tim Holloway (Molecular Genomics Core Facility, Peter MacCallum Cancer Centre) for provision of the NanoString nCounter Analysis System for gene expression profiling. The authors wish to acknowledge the work of pathologists Rod O'Keefe, John P. Dowling, and Sara Swain who reported patient outcomes in the original trial. We thank Tim Holloway and Gisela Mir Anau (Genomics Facility, Peter MacCallum Cancer Center) for their technical support, and Sonia Mailer (Melanoma Research Victoria) for her assistance.
Publisher Copyright:
© 2019 The Authors
PY - 2020/4
Y1 - 2020/4
N2 - Lentigo maligna (LM) is a common subtype of in situ melanoma on chronically sun-exposed skin, particularly the head and neck of older patients. Although surgery is the standard treatment, there is associated morbidity, and options such as imiquimod cream or radiotherapy may be used if surgery is refused or inappropriate. Complete response rates following imiquimod treatment are variable in the literature. The aim of this study was to evaluate the host immune response both before and following treatment with imiquimod to better identify likely responders. Paired pre- and post-imiquimod treatment specimens were available for 27 patients. Patients were treated with imiquimod 5 days per week for 12 weeks; at 16 weeks, lesions were excised for histological assessment. Of the 27 patients, 16 were responders and 11 failed to clear the disease. PDL1 protein expression was increased, accompanied by a unique gene signature in lesions from patients that subsequently histologically cleared LM by 16 weeks. This comprised 57 upregulated immune genes in signaling networks for antigen presentation, type I interferon signaling, and T-cell activation. This may represent an early responder group to imiquimod, and this unique gene signature potentially can be used as a biomarker of LM response to imiquimod.
AB - Lentigo maligna (LM) is a common subtype of in situ melanoma on chronically sun-exposed skin, particularly the head and neck of older patients. Although surgery is the standard treatment, there is associated morbidity, and options such as imiquimod cream or radiotherapy may be used if surgery is refused or inappropriate. Complete response rates following imiquimod treatment are variable in the literature. The aim of this study was to evaluate the host immune response both before and following treatment with imiquimod to better identify likely responders. Paired pre- and post-imiquimod treatment specimens were available for 27 patients. Patients were treated with imiquimod 5 days per week for 12 weeks; at 16 weeks, lesions were excised for histological assessment. Of the 27 patients, 16 were responders and 11 failed to clear the disease. PDL1 protein expression was increased, accompanied by a unique gene signature in lesions from patients that subsequently histologically cleared LM by 16 weeks. This comprised 57 upregulated immune genes in signaling networks for antigen presentation, type I interferon signaling, and T-cell activation. This may represent an early responder group to imiquimod, and this unique gene signature potentially can be used as a biomarker of LM response to imiquimod.
UR - https://www.scopus.com/pages/publications/85076843108
U2 - 10.1016/j.jid.2019.07.725
DO - 10.1016/j.jid.2019.07.725
M3 - Article
C2 - 31580843
AN - SCOPUS:85076843108
SN - 0022-202X
VL - 140
SP - 869-877.e16
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 4
ER -