Universität zu Köln

Failmezger, Henrik, Zwing, Natalie, Tresch, Achim ORCID: 0000-0002-4146-6371, Korski, Konstanty and Schmich, Fabian (2021). Computational Tumor Infiltration Phenotypes Enable the Spatial and Genomic Analysis of Immune Infiltration in Colorectal Cancer. Front. Oncol., 11. LAUSANNE: FRONTIERS MEDIA SA. ISSN 2234-943X

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Abstract

Cancer immunotherapy has led to significant therapeutic progress in the treatment of metastatic and formerly untreatable tumors. However, drug response rates are variable and often only a subgroup of patients will show durable response to a treatment. Biomarkers that help to select those patients that will benefit the most from immunotherapy are thus of crucial importance. Here, we aim to identify such biomarkers by investigating the tumor microenvironment, i.e., the interplay between different cell types like immune cells, stromal cells and malignant cells within the tumor and developed a computational method that determines spatial tumor infiltration phenotypes. Our method is based on spatial point pattern analysis of immunohistochemically stained colorectal cancer tumor tissue and accounts for the intra-tumor heterogeneity of immune infiltration. We show that, compared to base-line models, tumor infiltration phenotypes provide significant additional support for the prediction of established biomarkers in a colorectal cancer patient cohort (n = 80). Integration of tumor infiltration phenotypes with genetic and genomic data from the same patients furthermore revealed significant associations between spatial infiltration patterns and common mutations in colorectal cancer and gene expression signatures. Based on these associations, we computed novel gene signatures that allow one to predict spatial tumor infiltration patterns from gene expression data only and validated this approach in a separate dataset from the Cancer Genome Atlas.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Failmezger, Henrik UNSPECIFIED UNSPECIFIED UNSPECIFIED Zwing, Natalie UNSPECIFIED UNSPECIFIED UNSPECIFIED Tresch, Achim UNSPECIFIED orcid.org/0000-0002-4146-6371 UNSPECIFIED Korski, Konstanty UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmich, Fabian UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-569771
DOI:	10.3389/fonc.2021.552331
Journal or Publication Title:	Front. Oncol.
Volume:	11
Date:	2021
Publisher:	FRONTIERS MEDIA SA
Place of Publication:	LAUSANNE
ISSN:	2234-943X
Language:	English
Faculty:	Faculty of Medicine
Divisions:	Faculty of Medicine > Sonstiges > Zentrum für Versorgungsforschung Köln
Subjects:	Medical sciences Medicine
Uncontrolled Keywords:	Keywords Language DENSITY; COMPLEX; IMMUNOTHERAPY; INTERLEUKIN-7; EXPRESSION; DISCOVERY; SURVIVAL; PACKAGE Multiple languages Oncology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/56977