The emerging roles of Hedgehog signaling in tumor immune microenvironment

Juan Wang; Baiping Cui; Xiaojie Li; Xinyue Zhao; Taomin Huang; Xiaolei Ding

doi:10.3389/fonc.2023.1171418

The emerging roles of Hedgehog signaling in tumor immune microenvironment

Front Oncol. 2023 May 5:13:1171418. doi: 10.3389/fonc.2023.1171418. eCollection 2023.

Authors

Juan Wang^{1

2}, Baiping Cui^{1

2}, Xiaojie Li^{1

2}, Xinyue Zhao^{1

2}, Taomin Huang³, Xiaolei Ding^{1

2}

Affiliations

¹ Institute of Geriatrics, Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong), School of Medicine, Shanghai University, Nantong, China.
² Shanghai Engineering Research Center of Organ Repair, School of Medicine, Shanghai University, Shanghai, China.
³ Department of Pharmacy, Eye & ENT Hospital, Fudan University, Shanghai, China.

Abstract

The Hedgehog (Hh) signaling pathway is pervasively involved in human malignancies, making it an effective target for cancer treatment for decades. In addition to its direct role in regulating cancer cell attributes, recent work indicates that it has an immunoregulatory effect on tumor microenvironments. An integrated understanding of these actions of Hh signaling pathway in tumor cells and tumor microenvironments will pave the way for novel tumor treatments and further advances in anti-tumor immunotherapy. In this review, we discuss the most recent research about Hh signaling pathway transduction, with a particular emphasis on its role in modulating tumor immune/stroma cell phenotype and function, such as macrophage polarity, T cell response, and fibroblast activation, as well as their mutual interactions between tumor cells and nonneoplastic cells. We also summarize the recent advances in the development of Hh pathway inhibitors and nanoparticle formulation for Hh pathway modulation. We suggest that targeting Hh signaling effects on both tumor cells and tumor immune microenvironments could be more synergistic for cancer treatment.

Keywords: Hedgehog signaling pathway; cancer therapy; nanobiomaterials; tumor immunity; tumor microenvironment.

Publication types

Review

Grants and funding

This article is supported by the National Natural Science Foundation of China (No. 82272278, 82204450) and the Starting Grant of Shanghai University (XD).