Ropporin-1 and 1B Are Widely Expressed in Human Melanoma and Evoke Strong Humoral Immune Responses

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dc.contributor.authorDa Gama Duarte, Jessica
dc.contributor.authorWoods, Katherine
dc.contributor.authorQuigley, Luke T
dc.contributor.authorDeceneux, Cyril
dc.contributor.authorTutuka, Candani
dc.contributor.authorWitkowski, Tom
dc.contributor.authorOstrouska, Simone
dc.contributor.authorHudson, Chris
dc.contributor.authorTsao, Simon Chang-Hao
dc.contributor.authorPasam, Anupama
dc.contributor.authorDobrovic, Alexander
dc.contributor.authorBlackburn, Jonathan M
dc.contributor.authorCebon, Jonathan
dc.contributor.authorBehren, Andreas
dc.date.accessioned2021-10-14T14:37:54Z
dc.date.available2021-10-14T14:37:54Z
dc.date.issued2021-04-09
dc.date.updated2021-04-23T13:49:00Z
dc.description.abstractAntibodies 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 (<i>n</i> = 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 (<i>n</i> = 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.en_US
dc.identifierdoi: 10.3390/cancers13081805
dc.identifier.apacitationDa Gama Duarte, J., Woods, K., Quigley, L. T., Deceneux, C., Tutuka, C., Witkowski, T., ... Behren, A. (2021). Ropporin-1 and 1B Are Widely Expressed in Human Melanoma and Evoke Strong Humoral Immune Responses. <i>Cancers</i>, 13(8), 1805. http://hdl.handle.net/11427/35249en_ZA
dc.identifier.chicagocitationDa Gama Duarte, Jessica, Katherine Woods, Luke T Quigley, Cyril Deceneux, Candani Tutuka, Tom Witkowski, Simone Ostrouska, et al "Ropporin-1 and 1B Are Widely Expressed in Human Melanoma and Evoke Strong Humoral Immune Responses." <i>Cancers</i> 13, 8. (2021): 1805. http://hdl.handle.net/11427/35249en_ZA
dc.identifier.citationDa Gama Duarte, J., Woods, K., Quigley, L.T., Deceneux, C., Tutuka, C., Witkowski, T., Ostrouska, S. & Hudson, C. et al. 2021. Ropporin-1 and 1B Are Widely Expressed in Human Melanoma and Evoke Strong Humoral Immune Responses. <i>Cancers.</i> 13(8):1805. http://hdl.handle.net/11427/35249en_ZA
dc.identifier.ris TY - Journal Article AU - Da Gama Duarte, Jessica AU - Woods, Katherine AU - Quigley, Luke T AU - Deceneux, Cyril AU - Tutuka, Candani AU - Witkowski, Tom AU - Ostrouska, Simone AU - Hudson, Chris AU - Tsao, Simon Chang-Hao AU - Pasam, Anupama AU - Dobrovic, Alexander AU - Blackburn, Jonathan M AU - Cebon, Jonathan AU - Behren, Andreas AB - 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 (<i>n</i> = 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 (<i>n</i> = 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. DA - 2021-04-09 DB - OpenUCT DP - University of Cape Town IS - 8 J1 - Cancers LK - https://open.uct.ac.za PY - 2021 T1 - Ropporin-1 and 1B Are Widely Expressed in Human Melanoma and Evoke Strong Humoral Immune Responses TI - Ropporin-1 and 1B Are Widely Expressed in Human Melanoma and Evoke Strong Humoral Immune Responses UR - http://hdl.handle.net/11427/35249 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/35249
dc.identifier.vancouvercitationDa Gama Duarte J, Woods K, Quigley LT, Deceneux C, Tutuka C, Witkowski T, et al. Ropporin-1 and 1B Are Widely Expressed in Human Melanoma and Evoke Strong Humoral Immune Responses. Cancers. 2021;13(8):1805. http://hdl.handle.net/11427/35249.en_ZA
dc.language.isoenen_US
dc.publisher.departmentDepartment of Integrative Biomedical Sciencesen_US
dc.publisher.facultyFaculty of Health Sciencesen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.sourceCancersen_US
dc.source.journalissue8en_US
dc.source.journalvolume13en_US
dc.source.pagination1805en_US
dc.source.urihttps://www.mdpi.com/journal/cancers
dc.titleRopporin-1 and 1B Are Widely Expressed in Human Melanoma and Evoke Strong Humoral Immune Responsesen_US
dc.typeJournal Articleen_US
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