Universität zu Köln

Thelen, Martin ORCID: 0000-0002-2785-9726, Keller, Diandra, Lehmann, Jonas, Wennhold, Kerstin, Weitz, Hendrik, Bauer, Eugen, Gathof, Birgit, Brueggemann, Monika, Kotrova, Michaela, Quaas, Alexander, Mallmann, Christoph, Chon, Seung-Hun, Hillmer, Axel M., Bruns, Christiane, von Bergwelt-Baildon, Michael, Garcia-Marquez, Maria Alejandra and Schloesser, Hans Anton (2022). Immune responses against shared antigens are common in esophago-gastric cancer and can be enhanced using CD40-activated B cells. J. Immunother. Cancer, 10 (12). LONDON: BMJ PUBLISHING GROUP. ISSN 2051-1426

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Abstract

BackgroundSpecific immune response is a hallmark of cancer immunotherapy and shared tumor-associated antigens (TAAs) are important targets. Recent advances using combined cellular therapy against multiple TAAs renewed the interest in this class of antigens. Our study aims to determine the role of TAAs in esophago-gastric adenocarcinoma (EGA).MethodsRNA expression was assessed by NanoString in tumor samples of 41 treatment-nai''ve EGA patients. Endogenous T cell and antibody responses against the 10 most relevant TAAs were determined by FluoroSpot and protein-bound bead assays. Digital image analysis was used to evaluate the correlation of TAAs and T-cell abundance. T-cell receptor sequencing, in vitro expansion with autologous CD40-activated B cells (CD40Bs) and in vitro cytotoxicity assays were applied to determine specific expansion, clonality and cytotoxic activity of expanded T cells.Results68.3% of patients expressed >= 5 TAAs simultaneously with coregulated clusters, which were similar to data from The Cancer Genome Atlas (n=505). Endogenous cellular or humoral responses against >= 1 TAA were detectable in 75.0% and 53.7% of patients, respectively. We found a correlation of T-cell abundance and the expression of TAAs and genes related to antigen presentation. TAA-specific T-cell responses were polyclonal, could be induced or enhanced using autologous CD40Bs and were cytotoxic in vitro. Despite the frequent expression of TAAs co-occurrence with immune responses was rare.ConclusionsWe identified the most relevant TAAs in EGA for monitoring of clinical trials and as therapeutic targets. Antigen-escape rather than missing immune response should be considered as mechanism underlying immunotherapy resistance of EGA.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Thelen, Martin UNSPECIFIED orcid.org/0000-0002-2785-9726 UNSPECIFIED Keller, Diandra UNSPECIFIED UNSPECIFIED UNSPECIFIED Lehmann, Jonas UNSPECIFIED UNSPECIFIED UNSPECIFIED Wennhold, Kerstin UNSPECIFIED UNSPECIFIED UNSPECIFIED Weitz, Hendrik UNSPECIFIED UNSPECIFIED UNSPECIFIED Bauer, Eugen UNSPECIFIED UNSPECIFIED UNSPECIFIED Gathof, Birgit UNSPECIFIED UNSPECIFIED UNSPECIFIED Brueggemann, Monika UNSPECIFIED UNSPECIFIED UNSPECIFIED Kotrova, Michaela UNSPECIFIED UNSPECIFIED UNSPECIFIED Quaas, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED Mallmann, Christoph UNSPECIFIED UNSPECIFIED UNSPECIFIED Chon, Seung-Hun UNSPECIFIED UNSPECIFIED UNSPECIFIED Hillmer, Axel M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bruns, Christiane UNSPECIFIED UNSPECIFIED UNSPECIFIED von Bergwelt-Baildon, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Garcia-Marquez, Maria Alejandra UNSPECIFIED UNSPECIFIED UNSPECIFIED Schloesser, Hans Anton UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-684572
DOI:	10.1136/jitc-2022-005200
Journal or Publication Title:	J. Immunother. Cancer
Volume:	10
Number:	12
Date:	2022
Publisher:	BMJ PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	2051-1426
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language TUMOR-ASSOCIATED ANTIGENS; T-CELLS; GASTROESOPHAGEAL JUNCTION; PLUS CHEMOTHERAPY; PRESENTING CELLS; GENE-EXPRESSION; TESTIS ANTIGENS; ESOPHAGEAL; IDENTIFICATION; INFILTRATION Multiple languages Oncology; Immunology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/68457