HLA-DR cancer cells expression correlates with T cell infiltration and is enriched in lung adenocarcinoma with indolent behavior

Abstract Lung adenocarcinoma (ADC) is a heterogeneous group of tumors associated with different survival rates, even when detected at an early stage. Here, we aim to investigate whether CyTOF identifies cellular and molecular predictors of tumor behavior. We developed and validated a CyTOF panel of...

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Autores principales:	Maria-Fernanda Senosain, Yong Zou, Tatiana Novitskaya, Georgii Vasiukov, Aneri B. Balar, Dianna J. Rowe, Deon B. Doxie, Jonathan M. Lehman, Rosana Eisenberg, Fabien Maldonado, Andries Zijlstra, Sergey V. Novitskiy, Jonathan M. Irish, Pierre P. Massion
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6ab4fbb7ed444b2689b6cdcf1d62bde2
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spelling	oai:doaj.org-article:6ab4fbb7ed444b2689b6cdcf1d62bde22021-12-02T16:14:02ZHLA-DR cancer cells expression correlates with T cell infiltration and is enriched in lung adenocarcinoma with indolent behavior10.1038/s41598-021-93807-32045-2322https://doaj.org/article/6ab4fbb7ed444b2689b6cdcf1d62bde22021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-93807-3https://doaj.org/toc/2045-2322Abstract Lung adenocarcinoma (ADC) is a heterogeneous group of tumors associated with different survival rates, even when detected at an early stage. Here, we aim to investigate whether CyTOF identifies cellular and molecular predictors of tumor behavior. We developed and validated a CyTOF panel of 34 antibodies in four ADC cell lines and PBMC. We tested our panel in a set of 10 ADCs, classified into long- (LPS) (n = 4) and short-predicted survival (SPS) (n = 6) based on radiomics features. We identified cellular subpopulations of epithelial cancer cells (ECC) and their microenvironment and validated our results by multiplex immunofluorescence (mIF) applied to a tissue microarray (TMA) of LPS and SPS ADCs. The antibody panel captured the phenotypical differences in ADC cell lines and PBMC. LPS ADCs had a higher proportion of immune cells. ECC clusters (ECCc) were identified and uncovered two ADC groups. ECCc with high HLA-DR expression were correlated with CD4+ and CD8+ T cells, with LPS samples being enriched for those clusters. We confirmed a positive correlation between HLA-DR expression on ECC and T cell number by mIF staining on TMA slides. Spatial analysis demonstrated shorter distances from T cells to the nearest ECC in LPS. Our results demonstrate a distinctive cellular profile of ECC and their microenvironment in ADC. We showed that HLA-DR expression in ECC is correlated with T cell infiltration, and that a set of ADCs with high abundance of HLA-DR+ ECCc and T cells is enriched in LPS samples. This suggests new insights into the role of antigen presenting tumor cells in tumorigenesis.Maria-Fernanda SenosainYong ZouTatiana NovitskayaGeorgii VasiukovAneri B. BalarDianna J. RoweDeon B. DoxieJonathan M. LehmanRosana EisenbergFabien MaldonadoAndries ZijlstraSergey V. NovitskiyJonathan M. IrishPierre P. MassionNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Maria-Fernanda Senosain Yong Zou Tatiana Novitskaya Georgii Vasiukov Aneri B. Balar Dianna J. Rowe Deon B. Doxie Jonathan M. Lehman Rosana Eisenberg Fabien Maldonado Andries Zijlstra Sergey V. Novitskiy Jonathan M. Irish Pierre P. Massion HLA-DR cancer cells expression correlates with T cell infiltration and is enriched in lung adenocarcinoma with indolent behavior
description	Abstract Lung adenocarcinoma (ADC) is a heterogeneous group of tumors associated with different survival rates, even when detected at an early stage. Here, we aim to investigate whether CyTOF identifies cellular and molecular predictors of tumor behavior. We developed and validated a CyTOF panel of 34 antibodies in four ADC cell lines and PBMC. We tested our panel in a set of 10 ADCs, classified into long- (LPS) (n = 4) and short-predicted survival (SPS) (n = 6) based on radiomics features. We identified cellular subpopulations of epithelial cancer cells (ECC) and their microenvironment and validated our results by multiplex immunofluorescence (mIF) applied to a tissue microarray (TMA) of LPS and SPS ADCs. The antibody panel captured the phenotypical differences in ADC cell lines and PBMC. LPS ADCs had a higher proportion of immune cells. ECC clusters (ECCc) were identified and uncovered two ADC groups. ECCc with high HLA-DR expression were correlated with CD4+ and CD8+ T cells, with LPS samples being enriched for those clusters. We confirmed a positive correlation between HLA-DR expression on ECC and T cell number by mIF staining on TMA slides. Spatial analysis demonstrated shorter distances from T cells to the nearest ECC in LPS. Our results demonstrate a distinctive cellular profile of ECC and their microenvironment in ADC. We showed that HLA-DR expression in ECC is correlated with T cell infiltration, and that a set of ADCs with high abundance of HLA-DR+ ECCc and T cells is enriched in LPS samples. This suggests new insights into the role of antigen presenting tumor cells in tumorigenesis.
format	article
author	Maria-Fernanda Senosain Yong Zou Tatiana Novitskaya Georgii Vasiukov Aneri B. Balar Dianna J. Rowe Deon B. Doxie Jonathan M. Lehman Rosana Eisenberg Fabien Maldonado Andries Zijlstra Sergey V. Novitskiy Jonathan M. Irish Pierre P. Massion
author_facet	Maria-Fernanda Senosain Yong Zou Tatiana Novitskaya Georgii Vasiukov Aneri B. Balar Dianna J. Rowe Deon B. Doxie Jonathan M. Lehman Rosana Eisenberg Fabien Maldonado Andries Zijlstra Sergey V. Novitskiy Jonathan M. Irish Pierre P. Massion
author_sort	Maria-Fernanda Senosain
title	HLA-DR cancer cells expression correlates with T cell infiltration and is enriched in lung adenocarcinoma with indolent behavior
title_short	HLA-DR cancer cells expression correlates with T cell infiltration and is enriched in lung adenocarcinoma with indolent behavior
title_full	HLA-DR cancer cells expression correlates with T cell infiltration and is enriched in lung adenocarcinoma with indolent behavior
title_fullStr	HLA-DR cancer cells expression correlates with T cell infiltration and is enriched in lung adenocarcinoma with indolent behavior
title_full_unstemmed	HLA-DR cancer cells expression correlates with T cell infiltration and is enriched in lung adenocarcinoma with indolent behavior
title_sort	hla-dr cancer cells expression correlates with t cell infiltration and is enriched in lung adenocarcinoma with indolent behavior
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/6ab4fbb7ed444b2689b6cdcf1d62bde2
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HLA-DR cancer cells expression correlates with T cell infiltration and is enriched in lung adenocarcinoma with indolent behavior

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