CD24 May Serve as an Immunotherapy Target in Triple-Negative Breast Cancer by Regulating the Expression of PD-L1

Abstract

Purpose

CD24 mediates a “don’t eat me” signal to escape the immune environment. However, the correlation between CD24 and PD-L1 is unclear. This study aimed to assess if CD24 can serve as a target for immunotherapy of triple-negative breast cancer (TNBC).

Methods

Data on CD24 expression in breast cancer were acquired using the Oncomine and UALCAN tools. The role of CD24 expression on the prognosis of patients with TNBC was assessed using Kaplan–Meier analyses. Subsequently, STRING and TISIDB databases were used to construct protein–protein interaction networks and to explore immune-related molecules regulated by CD24. Immunofluorescence and immunohistochemistry assays were conducted to validate CD24 and PD-L1 expression and tumor infiltration lymphocyte (TIL) level. Survival analysis was also performed to explore the effect of CD24 and PD-L1 expression and TIL level in patients with TNBC. ShRNA was also used to explore the regulation role of CD24 on PD-L1 expression.

Results

CD24 expression was significantly higher in breast cancer than in normal tissues, with high expression being significantly associated with a worse prognosis. CD24 was found to be significantly regulated by chemokines, immunoinhibitors, immunostimulators and TILs. Furthermore, CD24 expression showed a significant positive correlation with PD-L1 expression and a negative correlation with TIL level. In association with PD-L1, CD24 was found to positively regulate lymphocyte costimulation, T cell costimulation, and leukocyte activation. Furthermore, CD24 and PD-L1 co-expression contributed to worse survival outcomes. In addition, CD24 expression was found to attenuate the positive effects of high-level TILs on the prognosis of patients with TNBC. CD24 can also regulate the expression of PD-L1 in TNBC cells.

Conclusion

CD24 may attenuate the positive effects of high TIL levels on survival and may facilitate the immune escape of TNBC by regulating PD-L1 expression. Thus, it is a potential target for immunotherapy in TNBC.

Keywords:

• triple negative breast cancer
• CD24
• PD-L1
• prognosis
• immunotherapy

Data Sharing Statement

These data and materials can be available from the corresponding author on reasonable request.

Ethics Approval and Informed Consent

The research was approved by the China Medical University Hospital institutional review board (2020PS282K). And the informed consent has obtained from the study participants prior to study commencement.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

These authors have declared that they have no competing interests.

Additional information

Funding

This study was supported by Doctoral Start-up Foundation of Liaoning Province (2023-BS-048).