A clinicopathological study on correlation between CD74+ fibroblasts and the formation of immunosuppressive microenvironment in oral squamous cell carcinoma

[Objective:] To investigate the expression of CD74+ fibroblasts in oral squamous cell carcinoma (OSCC) and their correlation with the immunosuppressive microenvironment of OSCC. [Methods:] The expression of CD74 of fibroblasts in OSCC tumor tissues and adjacent non-cancerous tissues will be detected...

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Main Authors: LIU Kunyu, ZHANG Qian, WANG Yuxin, YU Jiaxin, PU Yumei, YANG Xudong
Format: Article
Language:zho
Published: Editorial Office of Journal of Oral and Maxillofacial Surgery 2024-12-01
Series:Kouqiang hemian waike zazhi
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Online Access:https://journal06.magtech.org.cn/Jweb_joms/EN/10.12439/kqhm.1005-4979.2024.06.005
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author LIU Kunyu
ZHANG Qian
WANG Yuxin
YU Jiaxin
PU Yumei
YANG Xudong
author_facet LIU Kunyu
ZHANG Qian
WANG Yuxin
YU Jiaxin
PU Yumei
YANG Xudong
author_sort LIU Kunyu
collection DOAJ
description [Objective:] To investigate the expression of CD74+ fibroblasts in oral squamous cell carcinoma (OSCC) and their correlation with the immunosuppressive microenvironment of OSCC. [Methods:] The expression of CD74 of fibroblasts in OSCC tumor tissues and adjacent non-cancerous tissues will be detected using immunohistochemistry. The correlation between the expression of CD74 in cancer-associated fibroblasts (CAFs) and patients' clinicopathological parameters, prognosis, and immune cell infiltration will be further investigated. Primary CAFs, paired normal fibroblasts (NFs), and human peripheral blood mononuclear cells (PBMCs) from non-OSCC patients will be extracted to compare the differences in the expression of CD74 between the two types of fibroblasts. Subsequently, these two types of fibroblasts will be co-cultured with PBMCs, and the concentrations of interleukin-10 (IL-10) and IL-35 in the culture supernatant will be measured by enzyme-linked immunosorbent assay (ELISA). The effects of CAFs with different CD74 expression levels on the migration of PBMCs were compared by Transwell assay and flow cytometry. [Results:] The number of CD74+ fibroblasts in OSCC tumor tissues was significantly higher than that in adjacent non-cancerous tissues (P<0.001). Moreover, OSCC patients with high CD74 expression had a significantly lower 5-year overall survival rate (P<0.001). Immunohistochemical results showed that in tumor tissues with high CD74+ fibroblast expression, the ratio of FOXP3+ cells to CD4+ cells was significantly higher (P<0.001), and there was a significant positive correlation between the number of CD74+ fibroblasts and FOXP3+ cells (r=0.439 3). In vitro experiments confirmed that the expression of CD74 in primary CAFs from OSCC tumor tissues was higher than that in the paired NFs. After co-culturing with PBMCs for 12 h, the concentrations of IL-10 and IL-35 in the culture medium of the CAFs CD74 high-expression group were significantly higher than those in the NFs group (P<0.05). Additionally, the concentrations of IL-35 in the culture medium of the CAFs CD74 high-expression group were higher than those in the CAFs CD74 low-expression group (P<0.05). The results of flow cytometry showed that CAFs with high CD74 expression had a stronger chemotactic ability toward CD4+ FOXP3+ cells (P<0.05). [Conclusion:] CD74+ fibroblasts are associated with poorer prognosis in OSCC patients, and may be involved in the recruitment of CD4+ FOXP3+ cells.
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spelling doaj-art-2797f4010e93446191907e4e6bd4d5b62025-08-25T06:11:31ZzhoEditorial Office of Journal of Oral and Maxillofacial SurgeryKouqiang hemian waike zazhi1005-49792024-12-0134644245210.12439/kqhm.1005-4979.2024.06.005A clinicopathological study on correlation between CD74+ fibroblasts and the formation of immunosuppressive microenvironment in oral squamous cell carcinomaLIU Kunyu0ZHANG Qian1WANG Yuxin2YU Jiaxin3PU Yumei4YANG Xudong5Department of Oral and Maxillofacial Surgery, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing University, Nanjing 210008, ChinaDepartment of Oral and Maxillofacial Surgery, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing University, Nanjing 210008, ChinaDepartment of Oral and Maxillofacial Surgery, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing University, Nanjing 210008, ChinaDepartment of Oral and Maxillofacial Surgery, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing University, Nanjing 210008, ChinaDepartment of Oral and Maxillofacial Surgery, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing University, Nanjing 210008, ChinaDepartment of Oral and Maxillofacial Surgery, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing University, Nanjing 210008, China[Objective:] To investigate the expression of CD74+ fibroblasts in oral squamous cell carcinoma (OSCC) and their correlation with the immunosuppressive microenvironment of OSCC. [Methods:] The expression of CD74 of fibroblasts in OSCC tumor tissues and adjacent non-cancerous tissues will be detected using immunohistochemistry. The correlation between the expression of CD74 in cancer-associated fibroblasts (CAFs) and patients' clinicopathological parameters, prognosis, and immune cell infiltration will be further investigated. Primary CAFs, paired normal fibroblasts (NFs), and human peripheral blood mononuclear cells (PBMCs) from non-OSCC patients will be extracted to compare the differences in the expression of CD74 between the two types of fibroblasts. Subsequently, these two types of fibroblasts will be co-cultured with PBMCs, and the concentrations of interleukin-10 (IL-10) and IL-35 in the culture supernatant will be measured by enzyme-linked immunosorbent assay (ELISA). The effects of CAFs with different CD74 expression levels on the migration of PBMCs were compared by Transwell assay and flow cytometry. [Results:] The number of CD74+ fibroblasts in OSCC tumor tissues was significantly higher than that in adjacent non-cancerous tissues (P<0.001). Moreover, OSCC patients with high CD74 expression had a significantly lower 5-year overall survival rate (P<0.001). Immunohistochemical results showed that in tumor tissues with high CD74+ fibroblast expression, the ratio of FOXP3+ cells to CD4+ cells was significantly higher (P<0.001), and there was a significant positive correlation between the number of CD74+ fibroblasts and FOXP3+ cells (r=0.439 3). In vitro experiments confirmed that the expression of CD74 in primary CAFs from OSCC tumor tissues was higher than that in the paired NFs. After co-culturing with PBMCs for 12 h, the concentrations of IL-10 and IL-35 in the culture medium of the CAFs CD74 high-expression group were significantly higher than those in the NFs group (P<0.05). Additionally, the concentrations of IL-35 in the culture medium of the CAFs CD74 high-expression group were higher than those in the CAFs CD74 low-expression group (P<0.05). The results of flow cytometry showed that CAFs with high CD74 expression had a stronger chemotactic ability toward CD4+ FOXP3+ cells (P<0.05). [Conclusion:] CD74+ fibroblasts are associated with poorer prognosis in OSCC patients, and may be involved in the recruitment of CD4+ FOXP3+ cells.https://journal06.magtech.org.cn/Jweb_joms/EN/10.12439/kqhm.1005-4979.2024.06.005oral squamous cell carcinomafiborblastsimmunosuppressive microenviromentperipheral blood mononuclear cells
spellingShingle LIU Kunyu
ZHANG Qian
WANG Yuxin
YU Jiaxin
PU Yumei
YANG Xudong
A clinicopathological study on correlation between CD74+ fibroblasts and the formation of immunosuppressive microenvironment in oral squamous cell carcinoma
Kouqiang hemian waike zazhi
oral squamous cell carcinoma
fiborblasts
immunosuppressive microenviroment
peripheral blood mononuclear cells
title A clinicopathological study on correlation between CD74+ fibroblasts and the formation of immunosuppressive microenvironment in oral squamous cell carcinoma
title_full A clinicopathological study on correlation between CD74+ fibroblasts and the formation of immunosuppressive microenvironment in oral squamous cell carcinoma
title_fullStr A clinicopathological study on correlation between CD74+ fibroblasts and the formation of immunosuppressive microenvironment in oral squamous cell carcinoma
title_full_unstemmed A clinicopathological study on correlation between CD74+ fibroblasts and the formation of immunosuppressive microenvironment in oral squamous cell carcinoma
title_short A clinicopathological study on correlation between CD74+ fibroblasts and the formation of immunosuppressive microenvironment in oral squamous cell carcinoma
title_sort clinicopathological study on correlation between cd74 fibroblasts and the formation of immunosuppressive microenvironment in oral squamous cell carcinoma
topic oral squamous cell carcinoma
fiborblasts
immunosuppressive microenviroment
peripheral blood mononuclear cells
url https://journal06.magtech.org.cn/Jweb_joms/EN/10.12439/kqhm.1005-4979.2024.06.005
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