IFNγ signaling integrity in colorectal cancer immunity and immunotherapy

Wan Du; Timothy L Frankel; Michael Green; Weiping Zou

doi:10.1038/s41423-021-00735-3

IFNγ signaling integrity in colorectal cancer immunity and immunotherapy

Cell Mol Immunol. 2022 Jan;19(1):23-32. doi: 10.1038/s41423-021-00735-3. Epub 2021 Aug 12.

Authors

Wan Du^{1

2}, Timothy L Frankel¹, Michael Green^{2

3

4

5}, Weiping Zou^{6

7

8

9

10}

Affiliations

¹ Department of Surgery, University of Michigan School of Medicine, Ann Arbor, MI, USA.
² Center of Excellence for Cancer Immunology and Immunotherapy, Rogel Cancer Center, University of Michigan School of Medicine, Ann Arbor, MI, USA.
³ Department of Radiation Oncology, University of Michigan School of Medicine, Ann Arbor, MI, USA.
⁴ Veterans Affairs Ann Arbor Healthcare System, University of Michigan School of Medicine, Ann Arbor, MI, USA.
⁵ Graduate Programs in Immunology, University of Michigan School of Medicine, Ann Arbor, MI, USA.
⁶ Department of Surgery, University of Michigan School of Medicine, Ann Arbor, MI, USA. wzou@med.umich.edu.
⁷ Center of Excellence for Cancer Immunology and Immunotherapy, Rogel Cancer Center, University of Michigan School of Medicine, Ann Arbor, MI, USA. wzou@med.umich.edu.
⁸ Graduate Programs in Immunology, University of Michigan School of Medicine, Ann Arbor, MI, USA. wzou@med.umich.edu.
⁹ Tumor Biology, University of Michigan School of Medicine, Ann Arbor, MI, USA. wzou@med.umich.edu.
¹⁰ Department of Pathology, University of Michigan School of Medicine, Ann Arbor, MI, USA. wzou@med.umich.edu.

Abstract

The majority of colorectal cancer patients are not responsive to immune checkpoint blockade (ICB). The interferon gamma (IFNγ) signaling pathway drives spontaneous and ICB-induced antitumor immunity. In this review, we summarize recent advances in the epigenetic, genetic, and functional integrity of the IFNγ signaling pathway in the colorectal cancer microenvironment and its immunological relevance in the therapeutic efficacy of and resistance to ICB. Moreover, we discuss how to target IFNγ signaling to inform novel clinical trials to treat patients with colorectal cancer.

Keywords: ARID1A; Apoptosis; Colorectal cancer; EZH2; Ferroptosis; IFNGR; Immunity; Interferon; MHC; PD-1; PD-L1; Palmitoylation; T cell.

Publication types

Research Support, N.I.H., Extramural
Review

MeSH terms

Colorectal Neoplasms* / genetics
Colorectal Neoplasms* / therapy
Humans
Immunotherapy
Interferon-gamma* / metabolism
Protein Transport
Signal Transduction
Tumor Microenvironment

Substances

Interferon-gamma

Abstract

Publication types

MeSH terms

Substances

Grants and funding