The correlation between tumor-associated macrophage infiltration and progression in cervical carcinoma

Guo, Fan; Kong, Wei na; Zhao, Gang; Cheng, Zhen; Ai, Le; Lv, Jie; Feng, Yang; Ma, Xiumin

doi:10.1042/bsr20203145

Cited by 24 publications

(15 citation statements)

References 32 publications

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“…A high density of CD68+TAMs is associated with lymph node metastasis. 26 Under normal circumstances, dendritic cells promote the antitumor immune response of Th1/CTL and enhance the immune monitoring of tumor cells by secreting IL‐12. Studies have confirmed that an HPV16E5 protein‐targeted dendrite vaccine used in the treatment of tumor mice, controlled the growth of mouse tumors and improved the survival rate of mice.…”

Section: Discussionmentioning

confidence: 99%

Nocardia rubra cell‐wall skeleton influences the development of cervical carcinoma by promoting the antitumor effect of macrophages and dendritic cells

et al. 2022

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Background As an immune enhancer, Nocardia rubra cell‐wall skeleton (Nr‐CWS) has been used to treat persistent human papillomavirus infection and cervical precancerous lesions. However, it is still unclear whether it can be used to treat cervical carcinoma. Methods In our study, the aim was to determine whether Nr‐CWS affects the apoptosis of cervical carcinoma cells by enhancing the antitumor effect of dendritic cells and macrophages in vivo and in vitro. Results The experimental results showed that Nr‐CWS can promote the activity of dendritic cells and macrophages and reduce their apoptosis. It also increased the cytokines IL‐6, IL‐12, TNF‐ɑ, and IL‐1β secreted by dendritic cells and macrophages and reduced their PD‐L1 expression. In vitro, Nr‐CWS inhibited the proliferation, colony forming ability of HeLa and SiHa cervical carcinoma cell lines cultured with macrophages, and more cells were blocked in G2/M phase. Nr‐CWS promoted TNF‐ɑ/TNFR1/caspase‐8‐mediated apoptosis by increasing macrophages secretion of TNF‐ɑ and inhibited cell migration and invasion regulated by the WNT/β‐catenin‐EMT pathway. Nr‐CWS also reduced the expression of the cervical carcinoma genes E6 and E7 thereby increasing expression of p53 gene and decreasing expression of PD‐L1 gene. In vivo, Nr‐CWS inhibited tumor growth and decreased the expression of E6, E7, PD‐L1, P16, Ki67, and PCNA in tumors. Conclusions Therefore, our results suggest that Nr‐CWS can promote apoptosis of cervical carcinoma cells by enhancing the antitumor effect of dendritic cells and macrophages.

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Section: Discussionmentioning

confidence: 99%

Nocardia rubra cell‐wall skeleton influences the development of cervical carcinoma by promoting the antitumor effect of macrophages and dendritic cells

et al. 2022

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“…In Ovestad's study, CD160 was also downregulated in the CIN3/AIS lesions (45). The CD68 tumor-associated macrophages in CESC were significantly increased than those in normal tissue or paracarcinoma, and high stromal CD68 tumor-associated macrophages were born on lymph node metastasis (46). The upregulation of FUCA1 in SiHa is shown in Kalliopi's study (47).…”

Section: Discussionmentioning

confidence: 87%

Identification and validation of a novel necroptosis-related prognostic signature in cervical squamous cell carcinoma and endocervical adenocarcinoma

Zhang

Cao²,

Tong³

et al. 2022

Front. Oncol.

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Background: The purpose of this study was to investigate the prognostic signature of necroptosis-related lncRNAs (NRLs) and explore their association with immune-related functions and sensitivity of the therapeutic drug in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC).Methods: UCSC Xena provided lncRNA sequencing and clinical data about CESC, and a necroptosis gene list was obtained from the KEGG database. NRLs were selected by structuring a co-expression network of lncRNAs and necroptosis-related genes. To further screen lncRNAs, we used the univariate Cox regression method, Lasso regression, and multivariate Cox regression. Afterward, an NRL signature was established. We used the xCell algorithm and single-sample gene set enrichment analysis (ssGSEA) to clarify the pertinence between immune infiltration and NRL expressions in CESC patients and explored the relationship between the target lncRNAs and immune-related genes. By leveraging the GDSC database, the therapysensitive response of the prognostic signature was forecasted and an experimental validation was performed. We performed GSEA with the aim of recognizing the potential pathway related to the individual prognostic signature. Results:The two prognostic NRLs (AC009095.1 and AC005332.4) showed significant diversity and constituted the NRL signature. On the grounds of our signature, risk score was an independent element which was bound up with patient outcome (HR = 4.97 CI: 1.87-13.2, P = 0.001). The CESC patients were classified by the median risk score. Immune infiltration analysis revealed significant increases in CD4 + Tcm, eosinophils, epithelial cells, fibroblasts, Frontiers in Oncology frontiersin.org 01

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“…According to some studies, the number of macrophages increases with the progression of cervical neoplastic lesions [16,18,[20][21][22][23][24]. Tumor cells have been suggested to secrete various types of cytokines into the TME to promote monocyte migration to the neoplastic tissue.…”

Section: Discussionmentioning

confidence: 99%

Infiltration by Intratumor and Stromal CD8 and CD68 in Cervical Cancer

et al. 2023

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Background and Objectives: The tumor microenvironment (TME) plays a major role in neoplastic development. Various types of cells can be found in the TME. These cells can be classified into two groups, immunosuppressive and immunostimulatory types, depending on the function they perform in the antitumor immune response (IR). By interacting both with each other and with tumor cells, different immune mechanisms are activated or inhibited, which can suppress or promote the development and progression of cervical cancer (CC). Our aim was to investigate some of the main components of the cellular immune response in TME—tumor-infiltrating cytotoxic T cells (Tc, CD8+) and tumor-associated macrophages (TAMs, CD68+)—in patients with CC. Materials and Methods: We analyzed 72 paraffin-embedded tumor tissues of patients diagnosed and treated at Medical University Pleven, Bulgaria. Patients were classified according to the 2018 FIGO (International Federation of Gynaecology and Obstetrics) classification. From each patient, we selected one histological slide with hematoxylin eosin staining. In a microscopic evaluation, CD8+ T lymphocytes and CD68+-positive macrophages were counted in the tumor and stroma of five randomly selected fields at ×40 magnification (HPF). We analyzed the relationship between intratumoral and stromal CD8 and CD68 expression and FIGO stage and N status. Results: There was no significant association between the expression levels of intratumoral and stromal CD68+ cells in the different FIGO stages and according to the lymph nodes’ involvement. For CD8+ cells, the association of stromal infiltration was also not found, but T intratumor infiltration was associated with a higher FIGO stage, despite the fact that the results did not reach significance (p = 0.063, Fisher test). Intratumoral CD8+ cells were significantly associated with positive N status, (p = 0.035). Discussion: The separation of tumor-infiltrating cytotoxic T cells and tumor-associated macrophages into intratumoral and stromal is inconsequential. In our study, the level of infiltration of CD68+ cells in tumors and stromata was not significantly associated with tumor progression or lymph node involvement. The results were different for CD8+ cells, in which levels of infiltration were associated with lymph nodes’ statuses. Conclusions: The separate evaluation of CD68+ immune cells in the TME as intratumoral and stromal is not beneficial for defining prognoses, since the presence of these cells is not associated with the patient’s stage. In our study, the presence of CD8+ cells was significantly associated with lymph node metastases. The prognostic value of the obtained results can be enriched with an additional study of the lymphocyte phenotype, including B and other subtypes of T lymphocytes, NK cells, as well as molecules involved in the immune response, such as HLA subtypes.

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The correlation between tumor-associated macrophage infiltration and progression in cervical carcinoma

Cited by 24 publications

References 32 publications

Nocardia rubra cell‐wall skeleton influences the development of cervical carcinoma by promoting the antitumor effect of macrophages and dendritic cells

Nocardia rubra cell‐wall skeleton influences the development of cervical carcinoma by promoting the antitumor effect of macrophages and dendritic cells

Identification and validation of a novel necroptosis-related prognostic signature in cervical squamous cell carcinoma and endocervical adenocarcinoma

Infiltration by Intratumor and Stromal CD8 and CD68 in Cervical Cancer

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