Let-7i enhances anti-tumour immunity and suppresses ovarian tumour growth

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dc.contributor.authorWilkinson, A.N.
dc.contributor.authorChen, R.
dc.contributor.authorColeborn, E.
dc.contributor.authorNeilson, T.
dc.contributor.authorLe, K.
dc.contributor.authorBhavsar, C.
dc.contributor.authorWang, Y.
dc.contributor.authorAtluri, S.
dc.contributor.authorIrgam, G.
dc.contributor.authorWong, K.
dc.contributor.authorYang, D.
dc.contributor.authorSteptoe, R.
dc.contributor.authorWu, S.Y.
dc.date.issued2024
dc.description.abstractCancer immunotherapy has seen signifcant success in the last decade for cancer management by enhancing endogenous cancer immunity. However, immunotherapies developed thus far have seen limited success in the majority of high-grade serous carcinoma (HGSC) ovarian cancer patients. This is largely due to the highly immunosuppressive tumour microenvironment of HGSC and late-stage identifcation. Thus, novel treatment interventions are needed to overcome this immunosuppression and complement existing immunotherapies. Here, we have identifed through analysis of >600 human HGSC tumours a critical role for Let-7i in modulating the tumoural immune network. Tumoural expression of Let-7i had high positive correlation with anti-cancer immune signatures in HGSC patients. Confrming this role, enforced Let-7i expression in murine HGSC tumours resulted in a signifcant decrease in tumour burden with a signifcant increase in tumour T cell numbers in tumours. In concert with the improved tumoural immunity, Let-7i treatment also signifcantly increased CD86 expression in antigen presenting cells (APCs) in the draining lymph nodes, indicating enhanced APC activity. Collectively, our fndings highlight an important role of Let-7i in anti-tumour immunity and its potential use for inducing an anti-tumour efect in HGSC.
dc.description.statementofresponsibilityAndrew N. Wilkinson, Rui Chen, Elaina Coleborn, Trent Neilson, Khang Le, Chintan Bhavsar, Yue Wang, Sharat Atluri, Gowri Irgam, Kiefer Wong, Da Yang, Raymond Steptoe, Sherry Y. Wu
dc.identifier.citationCancer Immunology, Immunotherapy, 2024; 73(5):80-1-80-12
dc.identifier.doi10.1007/s00262-024-03674-w
dc.identifier.issn0340-7004
dc.identifier.issn0340-7004
dc.identifier.orcidChen, R. [0000-0003-4671-4538]
dc.identifier.urihttps://hdl.handle.net/2440/143571
dc.language.isoen
dc.publisherSpringer
dc.rights© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
dc.source.urihttps://doi.org/10.1007/s00262-024-03674-w
dc.subjectmiRNA; Let-7i; Cancer immunity; Ovarian cancer
dc.subject.meshT-Lymphocytes
dc.subject.meshAnimals
dc.subject.meshHumans
dc.subject.meshMice
dc.subject.meshOvarian Neoplasms
dc.subject.meshMicroRNAs
dc.subject.meshFemale
dc.subject.meshTumor Microenvironment
dc.titleLet-7i enhances anti-tumour immunity and suppresses ovarian tumour growth
dc.typeJournal article
pubs.publication-statusPublished

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