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N -glycosylation Regulates Intrinsic IFN-γ Resistance in Colorectal Cancer: Implications for Immunotherapy by Julia Krug; Gabriele Rodrian; Katja Petter; Hai Yang; Svetlana Khoziainova; Wei Guo; Alan Bénard; Susanne Merkel; Susan Gellert; Simone Maschauer; Monika Spermann; Maximilian Waldner; Peter Bailey; Christian Pilarsky; Andrea Liebl; Philipp Tripal; Jan Christoph; Elisabeth Naschberger; Roland Croner; Vera S. Schellerer; Christoph Becker; Arndt Hartmann; Thomas Tüting; Olaf Prante; Robert Grützmann; Sergei I. Grivennikov; Michael Stürzl; Nathalie Britzen-Laurent is a Medicine article available to read on EtoBox.

What is N -glycosylation Regulates Intrinsic IFN-γ Resistance in Colorectal Cancer: Implications for Immunotherapy about?

## BACKGROUND & AIMS: Advanced colorectal carcinoma (CRC) is characterized by a high frequency of primary immune evasion and refractoriness to immunotherapy. Given the importance of interferon (IFN)-γ in CRC immunosurveillance, we investigated whether and how acquired IFN-γ resistance in tumor cells would promote tumor growth, and whether IFN-γ sensitivity could be restored. ## METHODS: Spontaneous and colitis-associated CRC development was induced in mice with a specific IFN-γ pathway inhibition in intestinal epithelial cells. The influence of IFN-γ pathway gene status and expression on survival was assessed in patients with CRC. The mechanisms underlying IFN-γ resistance were investigated in CRC cell lines. ## RESULTS: The conditional knockout of the IFN-γ receptor in intestinal epithelial cells enhanced spontaneous and colitis-associated colon tumorigenesis in mice, and the loss of IFN-γ receptor __α__ (IFNγR__α__) expression by tumor cells predicted poor prognosis in patients with CRC. IFNγR__α__ expression was repressed in human CRC cells through changes in __N__-glycosylation, which decreased protein stability via proteasome-dependent degradation, inhibiting IFNγR-signaling.

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Author

Julia Krug; Gabriele Rodrian; Katja Petter; Hai Yang; Svetlana Khoziainova; Wei Guo; Alan Bénard; Susanne Merkel; Susan Gellert; Simone Maschauer; Monika Spermann; Maximilian Waldner; Peter Bailey; Christian Pilarsky; Andrea Liebl; Philipp Tripal; Jan Christoph; Elisabeth Naschberger; Roland Croner; Vera S. Schellerer; Christoph Becker; Arndt Hartmann; Thomas Tüting; Olaf Prante; Robert Grützmann; Sergei I. Grivennikov; Michael Stürzl; Nathalie Britzen-Laurent

Publisher

Elsevier BV

Published

2023

Language

EN

Field

Medicine (Health Sciences)