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CD22 is a potential target of CAR-NK cell therapy for esophageal squamous cell carcinoma

BACKGROUND: Chimeric antigen receptor NK (CAR-NK) cell therapy is one of the most promising immunotherapies. Although it has shown a significant therapeutic effect in hematologic malignancies, few successes have been obtained in solid tumors including esophageal squamous cell carcinoma (ESCC). The m...

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Autores principales: Liu, Tingdang, Dai, Ximing, Xu, Yien, Guan, Tian, Hong, Liangli, Zaib, Tahir, Zhou, Qi, Cheng, Ke, Zhou, Xiaoling, Ma, Changchun, Sun, Pingnan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10563326/
https://www.ncbi.nlm.nih.gov/pubmed/37817249
http://dx.doi.org/10.1186/s12967-023-04409-8
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author Liu, Tingdang
Dai, Ximing
Xu, Yien
Guan, Tian
Hong, Liangli
Zaib, Tahir
Zhou, Qi
Cheng, Ke
Zhou, Xiaoling
Ma, Changchun
Sun, Pingnan
author_facet Liu, Tingdang
Dai, Ximing
Xu, Yien
Guan, Tian
Hong, Liangli
Zaib, Tahir
Zhou, Qi
Cheng, Ke
Zhou, Xiaoling
Ma, Changchun
Sun, Pingnan
author_sort Liu, Tingdang
collection PubMed
description BACKGROUND: Chimeric antigen receptor NK (CAR-NK) cell therapy is one of the most promising immunotherapies. Although it has shown a significant therapeutic effect in hematologic malignancies, few successes have been obtained in solid tumors including esophageal squamous cell carcinoma (ESCC). The major reasons are lack of specific cell surface antigens and complex tumor microenvironment. Here we identify CD22, a well-known tumor surface marker in hematologic malignancies, is expressed in ESCC, possibly serving as a potential target of CAR-NK cell therapy. METHODS: The expression of 13 tumor cell surface antigens used clinically was analyzed in patients from The Cancer Genome Atlas (TCGA) database. Also, mRNA expression were detected in 2 ESCC cell lines and 2 patients samples by qCPR. Then according to Venn diagram, CD22 was selected for further investigation. Following this, the expression of CD22 by immunofluorescence (IF) in ESCC cell lines and by immunohistochemistry (IHC) in 87 cases of human ESCC samples was detected respectively. On the basis of H-score results, the correlation between CD22 expression and clinical parameters was analyzed. As a proof, the efficacy of CD22-targeted CAR-NK cells against ESCC cell lines was performed by a real-time cell analyzer (RTCA) platform. RESULTS: KYSE-140 and KYSE-150 cell lines displayed surface expression of CD22. IHC showed an 80.46% (70/87) positive rate in ESCC patient samples. Among these, cell membranous expression of CD22 was observed in 27.59% (24/87) patient samples. Through chi-square test, expression of CD22 in ESCC was associated with lymph node metastasis while it was no related to the depth of tumor invasion and clinical stage. Engineered CD22-targeted CAR-NK cells exhibited inhibitory growth capability against ESCC cell lines (p < 0.0001). CONCLUSIONS: CD22 is a potential tumor surface antigen capable of being targeted by CAR-NK cells in ESCC. And potential therapeutics for ESCC may be developed based on immune cells expressing anti-CD22 CAR. The study also indicates that CD22 CAR-NK cells could be used in other cancers and more in vivo experiments are needed. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-023-04409-8.
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spelling pubmed-105633262023-10-11 CD22 is a potential target of CAR-NK cell therapy for esophageal squamous cell carcinoma Liu, Tingdang Dai, Ximing Xu, Yien Guan, Tian Hong, Liangli Zaib, Tahir Zhou, Qi Cheng, Ke Zhou, Xiaoling Ma, Changchun Sun, Pingnan J Transl Med Research BACKGROUND: Chimeric antigen receptor NK (CAR-NK) cell therapy is one of the most promising immunotherapies. Although it has shown a significant therapeutic effect in hematologic malignancies, few successes have been obtained in solid tumors including esophageal squamous cell carcinoma (ESCC). The major reasons are lack of specific cell surface antigens and complex tumor microenvironment. Here we identify CD22, a well-known tumor surface marker in hematologic malignancies, is expressed in ESCC, possibly serving as a potential target of CAR-NK cell therapy. METHODS: The expression of 13 tumor cell surface antigens used clinically was analyzed in patients from The Cancer Genome Atlas (TCGA) database. Also, mRNA expression were detected in 2 ESCC cell lines and 2 patients samples by qCPR. Then according to Venn diagram, CD22 was selected for further investigation. Following this, the expression of CD22 by immunofluorescence (IF) in ESCC cell lines and by immunohistochemistry (IHC) in 87 cases of human ESCC samples was detected respectively. On the basis of H-score results, the correlation between CD22 expression and clinical parameters was analyzed. As a proof, the efficacy of CD22-targeted CAR-NK cells against ESCC cell lines was performed by a real-time cell analyzer (RTCA) platform. RESULTS: KYSE-140 and KYSE-150 cell lines displayed surface expression of CD22. IHC showed an 80.46% (70/87) positive rate in ESCC patient samples. Among these, cell membranous expression of CD22 was observed in 27.59% (24/87) patient samples. Through chi-square test, expression of CD22 in ESCC was associated with lymph node metastasis while it was no related to the depth of tumor invasion and clinical stage. Engineered CD22-targeted CAR-NK cells exhibited inhibitory growth capability against ESCC cell lines (p < 0.0001). CONCLUSIONS: CD22 is a potential tumor surface antigen capable of being targeted by CAR-NK cells in ESCC. And potential therapeutics for ESCC may be developed based on immune cells expressing anti-CD22 CAR. The study also indicates that CD22 CAR-NK cells could be used in other cancers and more in vivo experiments are needed. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-023-04409-8. BioMed Central 2023-10-10 /pmc/articles/PMC10563326/ /pubmed/37817249 http://dx.doi.org/10.1186/s12967-023-04409-8 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Liu, Tingdang
Dai, Ximing
Xu, Yien
Guan, Tian
Hong, Liangli
Zaib, Tahir
Zhou, Qi
Cheng, Ke
Zhou, Xiaoling
Ma, Changchun
Sun, Pingnan
CD22 is a potential target of CAR-NK cell therapy for esophageal squamous cell carcinoma
title CD22 is a potential target of CAR-NK cell therapy for esophageal squamous cell carcinoma
title_full CD22 is a potential target of CAR-NK cell therapy for esophageal squamous cell carcinoma
title_fullStr CD22 is a potential target of CAR-NK cell therapy for esophageal squamous cell carcinoma
title_full_unstemmed CD22 is a potential target of CAR-NK cell therapy for esophageal squamous cell carcinoma
title_short CD22 is a potential target of CAR-NK cell therapy for esophageal squamous cell carcinoma
title_sort cd22 is a potential target of car-nk cell therapy for esophageal squamous cell carcinoma
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10563326/
https://www.ncbi.nlm.nih.gov/pubmed/37817249
http://dx.doi.org/10.1186/s12967-023-04409-8
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