A Distinct Pretreatment Immune Gene Signature in Lentigo Maligna Is Associated with Imiquimod Response

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. 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.

Development and Validation of a 12-Gene Immune Relevant Prognostic Signature for Lung Adenocarcinoma Through Machine Learning Strategies

“…However, none of these studies investigated the immune infiltration pattern associated with the risk group. Although several immune-associated prognostic biomarkers have been proposed in gastric cancer and melanoma (49,50), the study concentrating on immune related signature is still absent in LUAD. The importance of understanding the immunological landscape of LUAD in a large cohort should never be neglected, since this observation might reveal the underlying mechanism of response and resistance to specific immunomodulatory agents and help to guide a more effective and precise immunotherapy regimen (51).…”

Accumulation of CD103+ CD8+ T cells in a cutaneous melanoma micrometastasis

“…Multiplex IHC was performed as per our previous study with minor modifications . Briefly, 3‐µ m ‐thick sections of formalin‐fixed, paraffin‐embedded tissue were cut onto Trajan Series 3 slides (Trajan Sci Med, Ringwood, VIC, Australia).…”

“…Multiplex IHC was performed as per our previous study with minor modifications. 28 Briefly, 3-µM-thick sections of formalin-fixed, paraffin-embedded tissue were cut onto Trajan Series 3 slides (Trajan Sci Med, Ringwood, VIC, Australia). Slides were then loaded onto a BOND RX fully automated research stainer (Leica Biosystems, Mount Waverley, VIC, Australia), and an optimised serial protocol consisting of dewaxing, heat-induced epitope retrieval, blocking with hydrogen peroxide, staining with primary antibodies and Opal polymer HRP, Opal TSA amplification, washing steps and DAPI counterstain was performed ( Table 1).…”

SnapshotDx Quiz: March 2020

“…e25 2. Which of the following is TRUE regarding the findings from the study by Halse et al (2019)? a. Lentigo maligna (LM) pretreatment biopsies showed a statistically significant difference in immune cell subset densities between the responders and non-responders to imiquimod treatment.…”

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e25 2. Which of the following is TRUE regarding the findings from the study by Halse et al (2019)? a. Lentigo maligna (LM) pretreatment biopsies showed a statistically significant difference in immune cell subset densities between the responders and non-responders to imiquimod treatment.b. In pretreatment biopsies, the area of the dermis occupied by PD-L1 positive cells was significantly increased in responders to imiquimod as compared with non-responders.c.

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