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Association of PD-L1 and IDO1 expression with JAK-STAT pathway activation in soft-tissue leiomyosarcoma

Takeshi Iwasaki1,2, Kenichi Kohashi1, Yu Toda1

  • 1Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Fukuoka, Japan.

Journal of Cancer Research and Clinical Oncology
|September 20, 2020
PubMed
Abstract

Insights

This study found that programmed death ligand 1 (PD-L1) and indoleamine 2,3-dioxygenase 1 (IDO1) expression correlates with JAK2 signaling in soft tissue leiomyosarcoma (LMS). Combined inhibition of these pathways may offer new treatment strategies for LMS.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Immune checkpoint inhibitors targeting programmed death ligand 1 (PD-L1) and indoleamine 2,3-dioxygenase 1 (IDO1) are investigated for various cancers.
  • Understanding the interplay of PD-L1, IDO1, and JAK2 signaling is crucial for developing effective therapies for soft tissue leiomyosarcoma (LMS).

Purpose of the Study:

  • To investigate the relationship between PD-L1, IDO1, and JAK2 expression in soft tissue leiomyosarcoma (LMS).
  • To elucidate the roles of these signaling pathways in LMS pathogenesis and potential therapeutic targeting.

Main Methods:

  • Analysis of next-generation sequencing data from 53 LMS patients to assess PD-L1, IDO1, and JAK2 gene amplification and mRNA expression.
  • In vitro studies using an LMS cell line to determine the effect of JAK-STAT pathway activation on PD-L1 and IDO1 expression.
  • Immunohistochemical staining of 69 LMS specimens for PD-L1, IDO1, TDO2, and phosphorylated JAK2 (pJAK2).

Main Results:

  • PD-L1 and IDO1 mRNA expression positively correlated with JAK2 and STAT1 mRNA expression in LMS.
  • IFN-γ induced IDO1 and PD-L1 expression in an LMS cell line, which was inhibited by JAK inhibitors.
  • TDO2 expression correlated with pJAK2 and IDO1 expression in LMS specimens.

Conclusions:

  • The findings suggest a functional link between PD-L1, IDO1, and the IFN-γ-JAK-STAT pathway in soft tissue LMS.
  • Combined inhibition of PD-1/PD-L1 or IDO1 with IFN-γ-JAK-STAT pathway inhibitors presents a potential therapeutic strategy for LMS.
Keywords:
Indoleamine 2,3-dioxygenase 1JAK–STAT pathwayProgrammed death ligand 1Soft tissue leiomyosarcoma

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