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

Haywood, 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
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Depositing User: LivePure Connector
Date Deposited: 03 Jul 2021 00:13
Last Modified: 26 Oct 2021 00:40
URI: https://ueaeprints.uea.ac.uk/id/eprint/80398
DOI: 10.1245/s10434-020-08713-1

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