Type I interferon signaling regulates myeloid and T cell crosstalk in the glioblastoma tumor microenvironment
Juhee Lim,
Jeongwoo La,
Hyeon Cheol Kim,
In Kang,
Byeong Hoon Kang,
Keun Bon Ku,
Yumin Kim,
Myoung Seung Kwon,
Heung Kyu Lee
Affiliations
Juhee Lim
Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea
Jeongwoo La
Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea; Laboratory of Host Defenses, Department of Biological Sciences, KAIST, Daejeon 34141, Republic of Korea
Hyeon Cheol Kim
Laboratory of Host Defenses, Department of Biological Sciences, KAIST, Daejeon 34141, Republic of Korea; Life Science Institute, KAIST, Daejeon 34141, Republic of Korea
In Kang
Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea; Laboratory of Host Defenses, Department of Biological Sciences, KAIST, Daejeon 34141, Republic of Korea
Byeong Hoon Kang
Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea; Laboratory of Host Defenses, Department of Biological Sciences, KAIST, Daejeon 34141, Republic of Korea
Keun Bon Ku
Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea; Laboratory of Host Defenses, Department of Biological Sciences, KAIST, Daejeon 34141, Republic of Korea; Center for Infectious Disease Vaccine and Diagnosis Innovation, Korea Research Institute of Chemical Technology, Daejeon 34114, Republic of Korea
Yumin Kim
Laboratory of Host Defenses, Department of Biological Sciences, KAIST, Daejeon 34141, Republic of Korea
Myoung Seung Kwon
Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea; Laboratory of Host Defenses, Department of Biological Sciences, KAIST, Daejeon 34141, Republic of Korea
Heung Kyu Lee
Laboratory of Host Defenses, Department of Biological Sciences, KAIST, Daejeon 34141, Republic of Korea; KAIST Institute of Health Science and Technology, KAIST, Daejeon 34141, Republic of Korea; Corresponding author
Summary: Downstream interferon signaling through the type I interferon (IFN) receptor, IFNAR, is crucial for the proper production of type I IFNs in mounting anti-tumor immune responses. Our study investigates the role of type I IFN signaling in the glioblastoma (GBM) tumor microenvironment by leveraging single-cell RNA sequencing to analyze tumor-infiltrating lymphocytes. We investigate how type I IFN signaling within the myeloid compartment contributes to the crosstalk with T cells in the tumor microenvironment. Through the use of the Gl261 murine GBM model, we find that the lack of proper type I IFN response results in enhanced PD-L1 interactions among myeloid cells, thereby affecting T cell functionality. Additionally, we also characterize how anti-PD1 treatment induces transcriptional changes in tumor-associated monocytes and macrophages by analyzing intercellular communication networks and propose how immune checkpoint blockade therapy could possibly relieve some of the immunosuppression derived from the lack of proper type I IFN production.
