Targeting LSD1 in tumor immunotherapy: rationale, challenges and potential

Lei Bao; Ping Zhu; Yuan Mou; Yinhong Song; Ye Qin

doi:10.3389/fimmu.2023.1214675

Targeting LSD1 in tumor immunotherapy: rationale, challenges and potential

Front Immunol. 2023 Jul 7:14:1214675. doi: 10.3389/fimmu.2023.1214675. eCollection 2023.

Authors

Lei Bao^{1

2}, Ping Zhu^{3

4}, Yuan Mou^{1

2}, Yinhong Song^{1

2

4}, Ye Qin^{1

2}

Affiliations

¹ Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, Yichang, China.
² College of Basic Medical Science, China Three Gorges University, Yichang, China.
³ Department of Nephrology, The First College of Clinical Medical Science, China Three Gorges University, Yichang, China.
⁴ Institute of Infection and Inflammation, China Three Gorges University, Yichang, China.

Abstract

Lysine-specific demethylase 1 (LSD1) is an enzyme that removes lysine methylation marks from nucleosome histone tails and plays an important role in cancer initiation, progression, metastasis, and recurrence. Recent research shows that LSD1 regulates tumor cells and immune cells through multiple upstream and downstream pathways, enabling tumor cells to adapt to the tumor microenvironment (TME). As a potential anti-tumor treatment strategy, immunotherapy has developed rapidly in the past few years. However, most patients have a low response rate to available immune checkpoint inhibitors (ICIs), including anti-PD-(L)1 therapy and CAR-T cell therapy, due to a broad array of immunosuppressive mechanisms. Notably, inhibition of LSD1 turns "cold tumors" into "hot tumors" and subsequently enhances tumor cell sensitivity to ICIs. This review focuses on recent advances in LSD1 and tumor immunity and discusses a potential therapeutic strategy for combining LSD1 inhibition with immunotherapy.

Keywords: LSD1; PD-(L)1; combination therapy; immunotherapy; tumor microenvironment.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Histone Demethylases / metabolism
Histones
Humans
Immunotherapy
Lysine*
Neoplasms* / therapy
Tumor Microenvironment

Substances

Lysine
Histone Demethylases
Histones

Grants and funding

This work was supported by The National Natural Science Foundation of China (No. 81671397), Hubei Provincial Department of Education Natural Science Research Project Fund (B2017024) and Yichang Medical and Health Research Project Fund (A20-2-002).