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ToolsHaywood, Sophia, Garioch, Jennifer, Ramaiya, Arjun and Moncrieff, Marc (2021) Quantitative and spatial analysis of CD8+/PD-1 tumor-infiltrating lymphocytes as a predictive biomarker for clinical response of melanoma in-transit metastases to topical immunotherapy. Annals of Surgical Oncology, 28 (2). pp. 1029-1038. ISSN 1068-9265
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Abstract
Background: Melanoma in-transit metastases (ITMs) are a challenge to treat and associated with systemic disease and poor prognosis. Topical diphencyprone (DPCP), a potent contact sensitizer, is an established treatment for melanoma ITMs. This exploratory study investigated the utility of BRAF mutation status, CD8, PD-1, PD-L1, and TILs distribution as biomarkers for response of ITMs to topical immunotherapy (DPCP). Methods: The ITM deposits of 40 patients treated with DPCP were subjected to biomarker analysis for BRAF status, CD8 and PD-1 expression on tumor-infiltrating lymphocytes (TILs), and tumor PD-L1 expression. Response to DPCP and overall survival (OS) were compared by biomarker status. Results: After 12 weeks, 10 patients (25%) had a complete response, 12 patients (30%) had a partial response, and 18 patients (45%) had no response. No significant association was found between any individual biomarker and response to DPCP or OS. The BRAF mutation rate was 25% (10/40). All the patients with a complete response had BRAF wild-type tumor. Peritumoral CD8+ T-cells were associated with complete response (P = 0.041). Both CD8+ and PD-1 expressions were highly correlated (P < 0.0001), and the highest levels of PD-1 expression were detected at the peritumoral interface (P = 0.0004). Only two cases were PD-L1-positive, and both had a complete response to DPCP (P = 0.043). Conclusion: Patients who have BRAF wild-type tumor are more likely to experience a complete response to DPCP. Peritumoral TILs and PD-1 expressions may predict a better response to DPCP. Expression of PD-L1 may be associated with a complete response to DPCP. A larger prospective study is required.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | surgery,oncology ,/dk/atira/pure/subjectarea/asjc/2700/2746 |
| Faculty \ School: | Faculty of Medicine and Health Sciences > Norwich Medical School |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 03 Jul 2021 00:13 |
| Last Modified: | 29 Jan 2024 03:16 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/80398 |
| DOI: | 10.1245/s10434-020-08713-1 |
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