scholarly journals A Study on the Correlation Between M2 Macrophages and Regulatory T Cells in the Progression of Colorectal Cancer

Author(s):  
Yanlei Chen ◽  
Yu Gao ◽  
Xueqian Ma ◽  
Yanping Wang ◽  
Jinhao Liu ◽  
...  

Abstract Background: M2 macrophages and regulatory T cells (Tregs) can promote tumors and development by inhibiting the anti-tumor immune response. This study investigated the number of CD163‐positive M2 macrophages and Foxp3-positive Tregs in the progression of colorectal cancer. It also investigated the correlation and of M2 macrophages and Tregs.Methods: Postoperative tissue specimens and clinical data were collected from 197 patients with colorectal cancer who underwent initial surgical treatment in The Second Ward of Colorectal Surgery of the First Affiliated Hospital of Jinzhou Medical University from March 2020 to December 2020. Use immunohistochemical methods to detect the expression levels of CD163 protein-labeled M2 macrophages and Foxp3 protein-labeled Tregs in colorectal cancer tissues, matched paracancer tissues and lymph node tissues. Analyze the correlation between CD163 and Foxp3 in cancer tissues and lymph node tissues, as well as the relationship between clinicopathological characteristics and preoperative tumor markers. Results: M2 macrophages and Tregs were significantly positively correlated in cancer and lymph node tissues, which significantly increased in cancer and metastatic lymph node tissues. Interestingly, M2 macrophages in non-metastatic lymph nodes also increased significantly in patients with metastatic lymph nodes. Tregs stage I+II is higher than stage III+IV in paraneoplastic tissues. In addition, both CD163 and Foxp3 were upregulated with increasing tumor TNM stage, depth of infiltration, lymphatic metastasis, and depth of infiltration, and both were positively correlated with CEA. Conclusion: M2 macrophages and Tregs are important indicators of colorectal cancer progression and lymph node metastasis. There is a certain correlation between the two types of cells. It is possible that M2 macrophages, together with suppressor cells Tregs, promote an immunosuppressive environment.

2021 ◽  
Author(s):  
Yanlei Chen ◽  
Chunyu Yang ◽  
Yue Wang ◽  
Xueqian Ma ◽  
Yanping Wang ◽  
...  

Abstract BackgroundColorectal cancer (CRC) is among the most common malignancies worldwide. M2 macrophages and regulatory T cells (Tregs) are immunosuppressive cells that can promote tumor progression via inhibiting anti-tumor immunities. However, the significance and correlation of the two types of cells in colorectal cancer are still inconclusive. The purpose of this study is to detect the number of M2 macrophages and Tregs in colorectal cancer and lymph nodes and to explore the clinical and pathological significance of their existence.MethodsThe pathologic specimens and clinical data of 197 patients with Colorectal cancer after radical resection were collected. Immunohistochemical methods were used to detect the expression of M2 macrophages and Tregs in colorectal cancer tissues, adjacent tissues, and lymph node tissues in each group.ResultsCompared with adjacent tissues and non-metastatic lymph node tissues, M2 macrophages and Tregs not only increased significantly in cancer tissues and metastatic lymph node tissues (P < 0.001), but also M2 macrophages in non-metastatic lymph node tissues adjacent to cancer tissues the number of phages expressed also increased significantly (P < 0.05). In addition, there was a positive correlation between the number of cancer tissues and lymph nodes (P < 0.001).ConclusionM2 macrophages are involved in the formation of lymph node immunosuppressive environment and promote the development of CRC and lymph node metastasis together with Tregs. Upregulation of M2 macrophages and Tregs expression is a prognostic marker for monitoring the condition of colorectal cancer and judging the prognosis.


2020 ◽  
Author(s):  
Yanping Wang ◽  
Jikun Wang ◽  
Jinhao Liu ◽  
Zuoxiu Shi ◽  
Yanlei Chen ◽  
...  

Abstract Background: Lymph node metastasis is a major prognostic factor of colorectal cancer and an important indicator for individualized treatment. M2 macrophages play a key role in carcinogenesis and tumor development, not only enhancing invasiveness, but also promoting lymph node metastasis. The purpose of this study was to investigate the effect of CD163-positive M2 macrophages on lymph node metastasis in colorectal cancer.Methods: Postoperative lymph node tissues were obtained from 120 patients with colorectal cancer who underwent radical surgery in the First Affiliated Hospital of Jinzhou Medical University between December 2019 and May 2020. We detected the expression of the CD163 protein in lymph nodes by immunohistochemistry. Furthermore, the relationship between M2 macrophages identified by this marker and lymph node metastasis were analyzed using the independent sample T-test and Chi-square test.Results: M2 macrophages were increased not only in metastatic lymph nodes, but also in non-metastatic lymph nodes adjacent to the cancer. The M2 macrophage count was higher in patients with macro-metastases than in those with micro-metastases.Conclusions: M2 macrophages represent an important factor for the promotion of lymph node metastasis in colorectal cancer, and may be a potential marker for its prediction. This may offer a new target for the comprehensive treatment of colorectal cancer.


2021 ◽  
Author(s):  
Kun Wu ◽  
Nan-nan Han ◽  
Sheng Zhang ◽  
Yan Li

Abstract Background: The presence of cervical lymph node metastasis is one of the poorest prognostic factors in oral squamous cell carcinoma (OSCC) with 50% reduction in survival of patients with lymph node positive involvement compared to those without. However, it is unknown whether immune checkpoint contributed to metastatic lymph nodes in OSCC patients. Methods: Flow cytometry and immunofluorescence staining were used to analyze the differences of CD4+ PD1+ T cells between metastatic and negative lymph nodes. RT-PCR was performed to clarify the expression of immune checkpoints and glycolysis related enzymes in metastatic and negative lymph nodes. Kruskal-Wallis tests, Mann-Whitney tests or nonparametric paired test (Wilcoxon matched paired test) were used to analyze the non-parametric distribution of samples. Results: We found that frequency of CD4+ T cells decreased in metastatic lymph nodes (p = 0.0019). In following experiments, immune checkpoints (PD1, PDL1 and CTLA4) of CD4+ T cells were detected in metastatic lymph node (LN+) and paired negative lymph node (LN-) of OSCC patients. The PD1 expression of LN+ was increased markedly compared to LN- (p = 0.0205). Similarly, the PD1 of CD4+ T cells in LN+ was increased significantly compared to LN-. We also found that glycolysis related enzymes levels in CD4+ T cells from LN+ were elevated dramatically compared to LN-. Moreover, PD1 and Hk2 expression of CD4+ T cells was increased in metastatic lymph nodes of OSCC patients with prior surgical treatment compared to those without. Conclusions: These findings suggested that increased PD1 and glycolysis in CD4+ T cell may serve as a pivotal regulator of OSCC metastatic lymph nodes via elevating glycolysis related enzymes level, especially in Hk2.


2021 ◽  
Author(s):  
Yanping Wang ◽  
Jikun Wang ◽  
Chunyu Yang ◽  
Yue Wang ◽  
Jinhao Liu ◽  
...  

Abstract Background: Lymph node metastasis is a major prognostic factor of colorectal carcinoma and an important indicator for individualized treatment. M2 macrophages play a key role in carcinogenesis and tumor development, not only enhancing invasiveness, but also promoting lymph node metastasis. The purpose of this study was to investigate the effect of CD163-positive M2 macrophages on lymph node metastasis in colorectal carcinoma.Methods: Postoperative lymph node tissues were obtained from 120 patients with colorectal carcinoma who underwent radical surgery in the First Affiliated Hospital of Jinzhou Medical University between December 2019 and May 2020. We detected the expression of the CD163 protein in lymph nodes by immunohistochemistry. Furthermore, the relationship between M2 macrophages identified by this marker and lymph node metastasis were analyzed using the independent sample T-test and Chi-square test.Results: M2 macrophages were increased not only in metastatic lymph nodes, but also in non-metastatic lymph nodes adjacent to the cancer. The M2 macrophage count was higher in patients with macro-metastases than in those with micro-metastases.Conclusions: M2 macrophages represent an important factor for the promotion of lymph node metastasis in colorectal carcinoma, and may be a potential marker for its prediction. This may offer a new target for the comprehensive treatment of colorectal carcinoma.


2019 ◽  
Author(s):  
Jun Ho Lee ◽  
Ju-Hee Lee ◽  
Byung Kyu Ahn ◽  
Seung Sam Paik ◽  
Hyunsung Kim ◽  
...  

Abstract Background The function of ASXL1 protein in colorectal cancer has not been investigated yet. The purpose of this study was to investigate the clinicopathological and prognostic impact of ASXL1 protein expression on colorectal cancer.Methods We performed immunohistochemical staining of ASXL1 protein using tissue microarrays of 408 colorectal cancers, 46 normal colonic mucosae, 48 adenomas, and 92 metastatic lymph nodes. The intensity of expression was scored as 0–3, and the extent of staining was scored as 0–4, based on the percentage of positive cells. The immunoreactivity score (IRS) was calculated by multiplying the two scores.Results ASXL1 protein expression rates were 89.1% in normal mucosae, 72.9% in tubular adenomas, 44.4% in adenocarcinomas, and 28.3% in metastatic lymph nodes ( p < 0.001). With respect to the IRS cut-off score, the mean tumor size was smaller in the IRS 0–6 group than in the IRS 8–12 group (4.9 ± 2.1 vs. 6.3 ± 2.7 cm, p = 0.002). Lymph node metastasis was more frequent in the IRS 0–6 group than in the IRS 8–12 group (56.3% vs. 33.3%, p = 0.034). Lymphatic invasion was more frequent in the 0–6 group than in the IRS 8–12 group (56.0% vs. 33.3%, p = 0.035). The 5-year disease-free survival rate did not differ between two groups at stage II and stage III.Conclusions ASXL1 protein might act as a tumor suppressor in colorectal cancer. The loss of ASXL1 expression might be associated with metastasis via the lymphatic system to the lymph nodes.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yanping Wang ◽  
Jikun Wang ◽  
Chunyu Yang ◽  
Yue Wang ◽  
Jinhao Liu ◽  
...  

Abstract Background Lymph node metastasis is a major prognostic sign of colorectal carcinoma and an important indicator for individualized treatment. M2 macrophages play a key role in carcinogenesis and tumor development by enhancing invasiveness and promoting lymph node metastasis. The purpose of this study was to investigate the effect of CD163-positive M2 macrophages on lymph node metastasis in colorectal carcinoma. Methods Postoperative lymph node tissues were obtained from 120 patients with colorectal carcinoma who underwent radical surgery in the First Affiliated Hospital of Jinzhou Medical University between December 2019 and May 2020. We detected the expression of the CD163 protein in lymph nodes using immunohistochemistry. Furthermore, the relationships between M2 macrophages identified by expression of CD163 and lymph node metastasis were analyzed using the independent sample t-test and Chi-square test. Results M2 macrophages were increased in metastatic lymph nodes and non-metastatic lymph nodes adjacent to the cancer. The M2 macrophage count was higher in patients with macro-metastases than in patients with micro-metastases. Conclusions The presence of M2 macrophages represents an important indicator for lymph node metastasis in colorectal carcinoma and may be a potential marker for its prediction. Thus, M2 macrophage localization might offer a new target for the comprehensive treatment of colorectal carcinoma.


2022 ◽  
Author(s):  
Kun Wu ◽  
Nan-nan Han ◽  
Sheng Zhang ◽  
Yan Li

Abstract Background: Cervical lymph node metastasis is one of the poorest prognostic factors in oral squamous cell carcinoma (OSCC). Activated immune cells and cancer cells generally have metabolic similarities in tumor microenvironment. However, it is unknown whether abnormal glycolysis in T cells could facilitate metastatic lymph nodes in patients with OSCC. Methods: Flow cytometry and immunofluorescence staining were used to analyze the differences in CD4+ PD1+ T cells between metastatic and negative lymph nodes. RT-PCR was performed to detail the expression of immune checkpoints and glycolysis-related enzymes in metastatic and negative lymph nodes. Kruskal-Wallis, Mann-Whitney, or nonparametric paired tests (i.e., the Wilcoxon matched paired test) were used to analyze the non-parametric distribution of the samples. Results: The frequency of CD4+ T cells decreased in the metastatic lymph nodes (p = 0.0019). Immune checkpoints (PD1, PDL1, and CTLA4) of CD4+ T cells were detected in metastatic (LN+) and paired negative lymph nodes (LN-) of OSCC patients. The PD1 expression of LN+ increased markedly compared to that of LN- (p = 0.0205). Similarly, the PD1 of CD4+ T cells in LN+ increased significantly compared to that of LN-. Glycolysis-related enzyme levels in CD4+ T cells from LN+ were dramatically higher than those in LN-. Moreover, PD1 and Hk2 expressions in CD4+ T cells increased in metastatic lymph nodes of OSCC patients with prior surgical treatment compared to those without. Conclusions: These findings suggest that increased PD1 and glycolysis in CD4+ T cells may serve as pivotal regulators of OSCC metastatic lymph nodes, which are closely associated with elevated glycolysis.


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