Neoantigens elicit T cell responses in breast cancer

Abstract Neoantigens are tumour-specific antigens that arise from non-synonymous mutations in tumour cells. However, their effect on immune responses in the tumour microenvironment remains unclear in breast cancer. We performed whole exome and RNA sequencing of 31 fresh breast cancer tissues and neo...

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Autores principales:	Takafumi Morisaki, Makoto Kubo, Masayo Umebayashi, Poh Yin Yew, Sachiko Yoshimura, Jae-Hyun Park, Kazuma Kiyotani, Masaya Kai, Mai Yamada, Yoshinao Oda, Yusuke Nakamura, Takashi Morisaki, Masafumi Nakamura
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2c8160b2daa6447d8caac1e64206aa46
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spelling	oai:doaj.org-article:2c8160b2daa6447d8caac1e64206aa462021-12-02T16:32:12ZNeoantigens elicit T cell responses in breast cancer10.1038/s41598-021-91358-12045-2322https://doaj.org/article/2c8160b2daa6447d8caac1e64206aa462021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-91358-1https://doaj.org/toc/2045-2322Abstract Neoantigens are tumour-specific antigens that arise from non-synonymous mutations in tumour cells. However, their effect on immune responses in the tumour microenvironment remains unclear in breast cancer. We performed whole exome and RNA sequencing of 31 fresh breast cancer tissues and neoantigen prediction from non-synonymous single nucleotide variants (nsSNVs) among exonic mutations. Neoantigen profiles were determined by predictive HLA binding affinity (IC50 < 500 nM) and mRNA expression with a read count of ≥ 1. We evaluated the association between neoantigen load and expression levels of immune-related genes. Moreover, using primary tumour cells established from pleural fluid of a breast cancer patient with carcinomatous pleurisy, we induced cytotoxic T lymphocytes (CTLs) by coculturing neoantigen peptide-pulsed dendritic cells (DCs) with autologous peripheral lymphocytes. The functions of CTLs were examined by cytotoxicity and IFN-γ ELISpot assays. Neoantigen load ranged from 6 to 440 (mean, 95) and was positively correlated to the total number of nsSNVs. Although no associations between neoantigen load and mRNA expression of T cell markers were observed, the coculture of neoantigen-pulsed DCs and lymphocytes successfully induced CTLs ex vivo. These results suggest that neoantigen analysis may have utility in developing strategies to elicit T cell responses.Takafumi MorisakiMakoto KuboMasayo UmebayashiPoh Yin YewSachiko YoshimuraJae-Hyun ParkKazuma KiyotaniMasaya KaiMai YamadaYoshinao OdaYusuke NakamuraTakashi MorisakiMasafumi NakamuraNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Takafumi Morisaki Makoto Kubo Masayo Umebayashi Poh Yin Yew Sachiko Yoshimura Jae-Hyun Park Kazuma Kiyotani Masaya Kai Mai Yamada Yoshinao Oda Yusuke Nakamura Takashi Morisaki Masafumi Nakamura Neoantigens elicit T cell responses in breast cancer
description	Abstract Neoantigens are tumour-specific antigens that arise from non-synonymous mutations in tumour cells. However, their effect on immune responses in the tumour microenvironment remains unclear in breast cancer. We performed whole exome and RNA sequencing of 31 fresh breast cancer tissues and neoantigen prediction from non-synonymous single nucleotide variants (nsSNVs) among exonic mutations. Neoantigen profiles were determined by predictive HLA binding affinity (IC50 < 500 nM) and mRNA expression with a read count of ≥ 1. We evaluated the association between neoantigen load and expression levels of immune-related genes. Moreover, using primary tumour cells established from pleural fluid of a breast cancer patient with carcinomatous pleurisy, we induced cytotoxic T lymphocytes (CTLs) by coculturing neoantigen peptide-pulsed dendritic cells (DCs) with autologous peripheral lymphocytes. The functions of CTLs were examined by cytotoxicity and IFN-γ ELISpot assays. Neoantigen load ranged from 6 to 440 (mean, 95) and was positively correlated to the total number of nsSNVs. Although no associations between neoantigen load and mRNA expression of T cell markers were observed, the coculture of neoantigen-pulsed DCs and lymphocytes successfully induced CTLs ex vivo. These results suggest that neoantigen analysis may have utility in developing strategies to elicit T cell responses.
format	article
author	Takafumi Morisaki Makoto Kubo Masayo Umebayashi Poh Yin Yew Sachiko Yoshimura Jae-Hyun Park Kazuma Kiyotani Masaya Kai Mai Yamada Yoshinao Oda Yusuke Nakamura Takashi Morisaki Masafumi Nakamura
author_facet	Takafumi Morisaki Makoto Kubo Masayo Umebayashi Poh Yin Yew Sachiko Yoshimura Jae-Hyun Park Kazuma Kiyotani Masaya Kai Mai Yamada Yoshinao Oda Yusuke Nakamura Takashi Morisaki Masafumi Nakamura
author_sort	Takafumi Morisaki
title	Neoantigens elicit T cell responses in breast cancer
title_short	Neoantigens elicit T cell responses in breast cancer
title_full	Neoantigens elicit T cell responses in breast cancer
title_fullStr	Neoantigens elicit T cell responses in breast cancer
title_full_unstemmed	Neoantigens elicit T cell responses in breast cancer
title_sort	neoantigens elicit t cell responses in breast cancer
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/2c8160b2daa6447d8caac1e64206aa46
work_keys_str_mv	AT takafumimorisaki neoantigenselicittcellresponsesinbreastcancer AT makotokubo neoantigenselicittcellresponsesinbreastcancer AT masayoumebayashi neoantigenselicittcellresponsesinbreastcancer AT pohyinyew neoantigenselicittcellresponsesinbreastcancer AT sachikoyoshimura neoantigenselicittcellresponsesinbreastcancer AT jaehyunpark neoantigenselicittcellresponsesinbreastcancer AT kazumakiyotani neoantigenselicittcellresponsesinbreastcancer AT masayakai neoantigenselicittcellresponsesinbreastcancer AT maiyamada neoantigenselicittcellresponsesinbreastcancer AT yoshinaooda neoantigenselicittcellresponsesinbreastcancer AT yusukenakamura neoantigenselicittcellresponsesinbreastcancer AT takashimorisaki neoantigenselicittcellresponsesinbreastcancer AT masafuminakamura neoantigenselicittcellresponsesinbreastcancer
_version_	1718383799723622400

Neoantigens elicit T cell responses in breast cancer

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