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

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          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.

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          Most cited references61

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            Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths that will occur in the United States and compiles the most recent data on population-based cancer occurrence. Incidence data (through 2016) were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data (through 2017) were collected by the National Center for Health Statistics. In 2020, 1,806,590 new cancer cases and 606,520 cancer deaths are projected to occur in the United States. The cancer death rate rose until 1991, then fell continuously through 2017, resulting in an overall decline of 29% that translates into an estimated 2.9 million fewer cancer deaths than would have occurred if peak rates had persisted. This progress is driven by long-term declines in death rates for the 4 leading cancers (lung, colorectal, breast, prostate); however, over the past decade (2008-2017), reductions slowed for female breast and colorectal cancers, and halted for prostate cancer. In contrast, declines accelerated for lung cancer, from 3% annually during 2008 through 2013 to 5% during 2013 through 2017 in men and from 2% to almost 4% in women, spurring the largest ever single-year drop in overall cancer mortality of 2.2% from 2016 to 2017. Yet lung cancer still caused more deaths in 2017 than breast, prostate, colorectal, and brain cancers combined. Recent mortality declines were also dramatic for melanoma of the skin in the wake of US Food and Drug Administration approval of new therapies for metastatic disease, escalating to 7% annually during 2013 through 2017 from 1% during 2006 through 2010 in men and women aged 50 to 64 years and from 2% to 3% in those aged 20 to 49 years; annual declines of 5% to 6% in individuals aged 65 years and older are particularly striking because rates in this age group were increasing prior to 2013. It is also notable that long-term rapid increases in liver cancer mortality have attenuated in women and stabilized in men. In summary, slowing momentum for some cancers amenable to early detection is juxtaposed with notable gains for other common cancers.
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                Author and article information

                Journal
                Breast Cancer (Dove Med Press)
                Breast Cancer (Dove Med Press)
                bctt
                Breast Cancer : Targets and Therapy
                Dove
                1179-1314
                28 December 2023
                2023
                : 15
                : 967-984
                Affiliations
                [1 ]Department of General Surgery, Cancer Hospital of China Medical University, Cancer Hospital of Dalian University of Technology, Liaoning Cancer Hospital and Institute , Shenyang, Liaoning, 110042, People’s Republic of China
                [2 ]Department of Oncology, Shengjing Hospital of China Medical University , Shenyang, Liaoning, 110004, People’s Republic of China
                [3 ]Department of Ultrasound, Shengjing Hospital of China Medical University , Shenyang, Liaoning, 110004, People’s Republic of China
                Author notes
                Correspondence: Jie Lin; Xudong Zhu, Department of General Surgery, Cancer Hospital of China Medical University, Cancer Hospital of Dalian University of Technology, Liaoning Cancer Hospital and Institute , Shenyang, Liaoning, 110042, People’s Republic of China, Tel +86 13940081800; +86 13354204706, Email linxiran0221@126.com; xdzhu@cmu.edu.cn
                Author information
                http://orcid.org/0000-0002-6657-6112
                Article
                409054
                10.2147/BCTT.S409054
                10758189
                38164371
                ccf7ffa5-3168-434d-938b-0e5272520821
                © 2023 Zhu et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 19 April 2023
                : 21 December 2023
                Page count
                Figures: 8, Tables: 3, References: 61, Pages: 18
                Funding
                Funded by: Doctoral Start-up Foundation of Liaoning Province, open-funder-registry 10.13039/501100010018;
                This study was supported by Doctoral Start-up Foundation of Liaoning Province (2023-BS-048).
                Categories
                Original Research

                triple negative breast cancer,cd24,pd-l1,prognosis,immunotherapy

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