Cancer-specific immune evasion and substantial heterogeneity within cancer types provide evidence for personalized immunotherapy
Martin Thelen, Kerstin Wennhold, Jonas Lehmann, María A. García-Márquez, Sebastian Klein, Elena Kochen, Philipp Lohneis, Axel Lechner, Svenja Wagener‐Ryczek, Patrick Sven Plum, Oscar Velázquez Camacho, David Pfister, F. Andrew Dorr, Matthias Heldwein, Khosro Hekmat, Dirk Beutner, Jens Peter Klußmann, Fabinshy Thangarajah, Dominik Ratiu, Wolfram Malter, Sabine Merkelbach‐Bruse, Christiane J. Bruns, Alexander Quaas, Michael von Bergwelt‐Baildon, Hans Schlößer
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.