Cancer-specific immune evasion and substantial heterogeneity within cancer types provide evidence for personalized immunotherapy

Abstract The immune response against cancer is orchestrated by various parameters and site-dependent specificities have been poorly investigated. In our analyses of ten different cancer types, we describe elevated infiltration by regulatory T cells as the most common feature, while other lymphocyte...

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Autores principales:	Martin Thelen, Kerstin Wennhold, Jonas Lehmann, Maria Garcia-Marquez, Sebastian Klein, Elena Kochen, Philipp Lohneis, Axel Lechner, Svenja Wagener-Ryczek, Patrick Sven Plum, Oscar Velazquez Camacho, David Pfister, Fabian Dörr, Matthias Heldwein, Khosro Hekmat, Dirk Beutner, Jens Peter Klussmann, Fabinshy Thangarajah, Dominik Ratiu, Wolfram Malter, Sabine Merkelbach-Bruse, Christiane Josephine Bruns, Alexander Quaas, Michael von Bergwelt-Baildon, Hans A. Schlößer
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/4edee7d56ead4b1585567524e79d56a7
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spelling	oai:doaj.org-article:4edee7d56ead4b1585567524e79d56a72021-12-02T17:40:05ZCancer-specific immune evasion and substantial heterogeneity within cancer types provide evidence for personalized immunotherapy10.1038/s41698-021-00196-x2397-768Xhttps://doaj.org/article/4edee7d56ead4b1585567524e79d56a72021-06-01T00:00:00Zhttps://doi.org/10.1038/s41698-021-00196-xhttps://doaj.org/toc/2397-768XAbstract The immune response against cancer is orchestrated by various parameters and site-dependent specificities have been poorly investigated. In our analyses of ten different cancer types, we describe elevated infiltration by regulatory T cells as the most common feature, while other lymphocyte subsets and also expression of immune-regulatory molecules on tumor-infiltrating lymphocytes showed site-specific variation. Multiparametric analyses of these data identified similarities of renal and liver or lung with head and neck cancer. Co-expression of immune-inhibitory ligands on tumor cells was most frequent in colorectal, lung and ovarian cancer. Genes related to antigen presentation were frequently dysregulated in liver and lung cancer. Expression of co-inhibitory molecules on tumor-infiltrating T cells accumulated in advanced stages while T-cell abundance was related to enhanced expression of genes related to antigen presentation. Our results promote evaluation of cancer-specific or even personalized immunotherapeutic combinations to overcome primary or secondary resistance as major limitation of immune-checkpoint inhibition.Martin ThelenKerstin WennholdJonas LehmannMaria Garcia-MarquezSebastian KleinElena KochenPhilipp LohneisAxel LechnerSvenja Wagener-RyczekPatrick Sven PlumOscar Velazquez CamachoDavid PfisterFabian DörrMatthias HeldweinKhosro HekmatDirk BeutnerJens Peter KlussmannFabinshy ThangarajahDominik RatiuWolfram MalterSabine Merkelbach-BruseChristiane Josephine BrunsAlexander QuaasMichael von Bergwelt-BaildonHans A. SchlößerNature PortfolioarticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Precision Oncology, Vol 5, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Martin Thelen Kerstin Wennhold Jonas Lehmann Maria Garcia-Marquez Sebastian Klein Elena Kochen Philipp Lohneis Axel Lechner Svenja Wagener-Ryczek Patrick Sven Plum Oscar Velazquez Camacho David Pfister Fabian Dörr Matthias Heldwein Khosro Hekmat Dirk Beutner Jens Peter Klussmann Fabinshy Thangarajah Dominik Ratiu Wolfram Malter Sabine Merkelbach-Bruse Christiane Josephine Bruns Alexander Quaas Michael von Bergwelt-Baildon Hans A. Schlößer Cancer-specific immune evasion and substantial heterogeneity within cancer types provide evidence for personalized immunotherapy
description	Abstract The immune response against cancer is orchestrated by various parameters and site-dependent specificities have been poorly investigated. In our analyses of ten different cancer types, we describe elevated infiltration by regulatory T cells as the most common feature, while other lymphocyte subsets and also expression of immune-regulatory molecules on tumor-infiltrating lymphocytes showed site-specific variation. Multiparametric analyses of these data identified similarities of renal and liver or lung with head and neck cancer. Co-expression of immune-inhibitory ligands on tumor cells was most frequent in colorectal, lung and ovarian cancer. Genes related to antigen presentation were frequently dysregulated in liver and lung cancer. Expression of co-inhibitory molecules on tumor-infiltrating T cells accumulated in advanced stages while T-cell abundance was related to enhanced expression of genes related to antigen presentation. Our results promote evaluation of cancer-specific or even personalized immunotherapeutic combinations to overcome primary or secondary resistance as major limitation of immune-checkpoint inhibition.
format	article
author	Martin Thelen Kerstin Wennhold Jonas Lehmann Maria Garcia-Marquez Sebastian Klein Elena Kochen Philipp Lohneis Axel Lechner Svenja Wagener-Ryczek Patrick Sven Plum Oscar Velazquez Camacho David Pfister Fabian Dörr Matthias Heldwein Khosro Hekmat Dirk Beutner Jens Peter Klussmann Fabinshy Thangarajah Dominik Ratiu Wolfram Malter Sabine Merkelbach-Bruse Christiane Josephine Bruns Alexander Quaas Michael von Bergwelt-Baildon Hans A. Schlößer
author_facet	Martin Thelen Kerstin Wennhold Jonas Lehmann Maria Garcia-Marquez Sebastian Klein Elena Kochen Philipp Lohneis Axel Lechner Svenja Wagener-Ryczek Patrick Sven Plum Oscar Velazquez Camacho David Pfister Fabian Dörr Matthias Heldwein Khosro Hekmat Dirk Beutner Jens Peter Klussmann Fabinshy Thangarajah Dominik Ratiu Wolfram Malter Sabine Merkelbach-Bruse Christiane Josephine Bruns Alexander Quaas Michael von Bergwelt-Baildon Hans A. Schlößer
author_sort	Martin Thelen
title	Cancer-specific immune evasion and substantial heterogeneity within cancer types provide evidence for personalized immunotherapy
title_short	Cancer-specific immune evasion and substantial heterogeneity within cancer types provide evidence for personalized immunotherapy
title_full	Cancer-specific immune evasion and substantial heterogeneity within cancer types provide evidence for personalized immunotherapy
title_fullStr	Cancer-specific immune evasion and substantial heterogeneity within cancer types provide evidence for personalized immunotherapy
title_full_unstemmed	Cancer-specific immune evasion and substantial heterogeneity within cancer types provide evidence for personalized immunotherapy
title_sort	cancer-specific immune evasion and substantial heterogeneity within cancer types provide evidence for personalized immunotherapy
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/4edee7d56ead4b1585567524e79d56a7
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Cancer-specific immune evasion and substantial heterogeneity within cancer types provide evidence for personalized immunotherapy

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