Multimodal profiling of pancreatic cancer reveals a TIMP-1-dominated secretory profile determining pro-tumor immunoinstruction in human cancers

Cell Reports Medicine 2026 Open access

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Authors: Julian Frädrich, Carmen Mota Reyes, Michel Hendel, Vanessa Brunner, Batu Toledo, Damjan Manevski, Alexander Sommer, Daniel Häußler, Dominik Beck, Daniele Lucarelli, Jaime Martínez de Villareal, Lennard Halle
+14 more Raphael Kfuri-Rubens, Kaan Çifcibaşı, Anna Hirschberger, Rupert Öllinger, Percy Alexander Knolle, Katja Steiger, Roland Rad, Fabian J. Theis, Francisco X. Real, Stefanie Bärthel, Jan P. Böttcher, Dieter Saur, İhsan Ekin Demir, Achim Krüger
DOI: 10.1016/j.xcrm.2025.102546
Cited by: 1
References: 100

Abstract

basal-like PC, and causal for PC-cell-mediated NK cell suppression, reflected by impaired cytotoxicity, interleukin-2 (IL-2) responses, and mammalian target of rapamycin (mTOR) signaling. In pre-clinical PC, TIMP-1/CISS proves targetable through combined inhibition of upstream kinases with clinically approved drugs trametinib and nintedanib. Collectively, CISS represents a ubiquitous signature of pro-tumor immunoinstruction with actionable diagnostic and therapeutic potential across human cancers.

Fields of Study & Subjects

Protease and Inhibitor Mechanisms Pancreatic and Hepatic Oncology Research Immune cells in cancer

Publication details

Journal / source
Cell Reports Medicine
Publisher
Elsevier BV
Volume
7
Issue
1
Pages
102546–102546
Publication date
1 January 2026
Language
EN