La Trobe
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Ropporin‐1 and 1b are widely expressed in human melanoma and evoke strong humoral immune responses

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journal contribution
posted on 06.07.2021, 03:56 by Jessica da Gama Duarte, K Woods, Luke Quigley, C Deceneux, C Tutuka, T Witkowski, Simone Ostrouska, C Hudson, SCH Tsao, A Pasam, Alexander Dobrovic, JM Blackburn, Jonathan Cebon, Andreas Behren
Antibodies that block immune regulatory checkpoints (programmed cell death 1, PD‐1 and cytotoxic T‐lymphocyte‐associated antigen 4, CTLA‐4) to mobilise immunity have shown unprecedented clinical efficacy against cancer, demonstrating the importance of antigen‐specific tumour recognition. Despite this, many patients still fail to benefit from these treatments and additional approaches are being sought. These include mechanisms that boost antigen‐specific immunity either by vaccination or adoptive transfer of effector cells. Other than neoantigens, epigenetically regulated and shared antigens such as NY‐ESO‐1 are attractive targets; however, tissue expression is often heterogeneous and weak. Therefore, peptide‐specific therapies combining multiple antigens rationally selected to give additive anti‐cancer benefits are necessary to achieve optimal outcomes. Here, we show that Ropporin‐1 (ROPN1) and 1B (ROPN1B), cancer restricted antigens, are highly expressed and immunogenic, inducing humoral immunity in patients with advanced metastatic melanoma. By multispectral immunohistochemistry, 88.5% of melanoma patients tested (n = 54/61) showed ROPN1B expression in at least 1 of 2/3 tumour cores in tissue microarrays. Antibody responses against ROPN1A and ROPN1B were detected in 71.2% of melanoma patients tested (n = 74/104), with increased reactivity seen with more advanced disease stages. Thus, ROPN1A and ROPN1B may indeed be viable targets for cancer immunotherapy, alone or in combination with other cancer antigens, and could be combined with additional therapies such as immune checkpoint blockade.

Funding

This project was partially funded by a Clinical and Laboratory Integration Program (CLIP) grant from the Cancer Research Institute (CRI). This project was also funded in part by the Ludwig Institute for Cancer Research, Melanoma Research Alliance (MRA) and the Melbourne Research Victoria (MRV). The Olivia Newton-John Cancer Research Institute acknowledges the support of the Victorian Government Operational Infrastructure Support Program and the Ian Potter Foundation for providing funds to purchase the Vectra System. The contents of the published material are solely the responsibility of La Trobe University and do not reflect the views of Cancer Australia. J.D.G.D. is supported by Cure Cancer Australia through the Cancer Australia Priority-driven Cancer Research Scheme (#1187815). J.M.B. is supported by a research chair from the National Research Foundation (South Africa). A.B. is supported by a fellowship from the Department of Health and Human Services acting through the Victorian Cancer Agency (VCA).

History

Publication Date

02/04/2021

Journal

Cancers

Volume

13

Issue

8

Article Number

ARTN 1805

Pagination

15p.

Publisher

MDPI

ISSN

2072-6694

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