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Title: A distinct pre-treatment immune gene signature in lentigo maligna is associated with imiquimod response.
Austin Authors: Halse, Heloise;Caramia, Franco;McLean, Catriona A;Wang, Minyu;Aw Yeang, Han Xian;Keam, Simon P;Behren, Andreas;Ly, Lena;Haskett, Martin;Cebon, Jonathan S ;McArthur, Grant A;Neeson, Paul J;Mar, Victoria J
Affiliation: Cancer Immunology Research, Peter MacCallum Cancer Centre, VCCC
Bioinformatics, Peter MacCallum Cancer Centre, VCCC
Department of Anatomical Pathology, Alfred Hospital
Cancer Immunology Research, Peter MacCallum Cancer Centre, VCCC; Sir Peter MacCallum Department of Oncology, University of Melbourne
Cancer Immunology Research, Peter MacCallum Cancer Centre, VCCC
School of Cancer Medicine, La Trobe University, Bundoora
Victorian Melanoma Service, Alfred Hospital
Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia
Austin Health, Heidelberg, Victoria, Australia
Sir Peter MacCallum Department of Oncology, University of Melbourne
School of Public Health and Preventive Medicine, Monash University
Issue Date: Apr-2020
Date: 2019-09-30
Publication information: The Journal of investigative dermatology 2020; 140(4): 869-877.e16
Abstract: Lentigo Maligna (LM) is a common subtype of in-situ melanoma on chronically sun-exposed skin, particularly the head and neck of older patients. Whilst 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 prior to 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. 16 of the 27 patients 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 up-regulated 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 can potentially be used as a biomarker of LM response to imiquimod.
DOI: 10.1016/j.jid.2019.07.725
ORCID: 0000-0002-3898-950X
Journal: The Journal of investigative dermatology
PubMed URL: 31580843
Type: Journal Article
Subjects: Lentigo maligna
T cells
dendritic cells
gene expression profile
Appears in Collections:Journal articles

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