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
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Acceso en línea:https://doaj.org/article/4edee7d56ead4b1585567524e79d56a7
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Sumario: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.