Targeting LSD1 in tumor immunotherapy: rationale, challenges and potential

Area of Science:

• Biochemistry
• Immunology
• Oncology

Background:

• Lysine-specific demethylase 1 (LSD1) is crucial in cancer development and progression.
• LSD1 influences tumor cells and immune cells within the tumor microenvironment (TME).
• Current immunotherapies, such as immune checkpoint inhibitors (ICIs), show limited efficacy in many patients due to tumor-induced immunosuppression.

Purpose of the Study:

• To review recent advancements in understanding LSD1's role in tumor immunity.
• To explore the potential of combining LSD1 inhibition with immunotherapy for cancer treatment.

Main Methods:

• Literature review of recent research on LSD1, tumor immunity, and immunotherapy.
• Analysis of mechanisms by which LSD1 affects the tumor microenvironment and immune response.
• Discussion of preclinical and clinical evidence for LSD1 inhibition in combination with ICIs.

Main Results:

• LSD1 inhibition can reprogram the tumor microenvironment from "cold" to "hot," increasing immune cell infiltration.
• LSD1 blockade enhances the sensitivity of tumor cells to immune checkpoint inhibitors (anti-PD-(L)1) and CAR-T cell therapy.
• LSD1 plays a significant role in regulating both tumor cell adaptation and immune cell function within the TME.

Conclusions:

• LSD1 inhibition represents a promising strategy to overcome resistance to current immunotherapies.
• Combining LSD1 inhibitors with ICIs may offer a more effective approach to cancer treatment.
• Further research into LSD1-targeted therapies is warranted to improve patient outcomes in oncology.