scholarly journals Increased Levels of PD1 and Glycolysis in CD4+ T Cells Promote Lymph Node Metastasis in Oral Squamous Cell Carcinoma Patients

2022 ◽  
Author(s):  
Kun Wu ◽  
Nan-nan Han ◽  
Sheng Zhang ◽  
Yan Li
Keyword(s):  
Squamous Cell Carcinoma ◽  
T Cells ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Cd4 T Cells ◽  
Immune Checkpoints ◽  
Metastatic Lymph Nodes ◽  
Node Metastasis ◽  
Metastatic Lymph ◽  
Negative Lymph Nodes

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.

Increased PD1 and Glycolysis in CD4+ T Cell Promotes Lymph Node Metastasis in Oral Squamous Cell Carcinoma Patients

2021 ◽  
Author(s):  
Kun Wu ◽  
Nan-nan Han ◽  
Sheng Zhang ◽  
Yan Li
Keyword(s):  
Squamous Cell Carcinoma ◽  
T Cells ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Cd4 T Cell ◽  
Immune Checkpoints ◽  
Metastatic Lymph Nodes ◽  
Node Metastasis ◽  
Metastatic Lymph ◽  
Negative Lymph Nodes

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.

scholarly journals Increased PD1 and Glycolysis in CD4+ T Cell Promotes Lymph Node Metastasis in Oral Squamous Cell Carcinoma Patients

2020 ◽  
Author(s):  
Kun Wu ◽  
Nan-nan Han ◽  
Sheng Zhang ◽  
Yan Li
Keyword(s):  
Squamous Cell Carcinoma ◽  
T Cells ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Oral Squamous Cell Carcinoma ◽  
Lymph Nodes ◽  
Cd4 T Cell ◽  
Metastatic Lymph Nodes ◽  
Node Metastasis ◽  
Metastatic Lymph

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. 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.

scholarly journals A Study of the Correlation Between M2 Macrophages and Lymph Node Metastasis of Colorectal Cancer

2020 ◽  
Author(s):  
Yanping Wang ◽  
Jikun Wang ◽  
Jinhao Liu ◽  
Zuoxiu Shi ◽  
Yanlei Chen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Lymph Nodes ◽  
Comprehensive Treatment ◽  
M2 Macrophage ◽  
M2 Macrophages ◽  
Metastatic Lymph Nodes ◽  
Node Metastasis ◽  
Metastatic Lymph

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.

scholarly journals Distribution pattern and prognosis of metastatic lymph nodes in cervical posterior to level V in nasopharyngeal carcinoma patients

2020 ◽  
Author(s):  
Chaoyang Jiang ◽  
Ji Ma ◽  
Hui Gao ◽  
Ling Zhang ◽  
Hua Li ◽  
...  
Keyword(s):  
Lymph Node ◽  
Nasopharyngeal Carcinoma ◽  
Lymph Node Metastasis ◽  
Lymph Nodes ◽  
Distribution Pattern ◽  
Cervical Region ◽  
Target Area ◽  
Metastatic Lymph Nodes ◽  
Node Metastasis ◽  
Metastatic Lymph

Abstract Background:Lymph node metastasis in the cervical region posterior to level V (PLV) often occurs in patients with nasopharyngeal carcinoma (NPC), but the significance of lymph node metastasis in this region and the delineation of the radiotherapy target area have not been reported. We aimed to explore the distribution pattern and prognosis of metastatic lymph nodes in the PLV region in patients with NPC.Methods:We retrospectively studied 605 cases of NPC diagnosed by pathology from December 2011 to November 2017. All patients were subjected to an enhanced CT scan from the cranial apex to 2 cm below the sternoclavicular joints. The nodal distribution at each level was assessed in accordance with the Radiation Therapy Oncology Group (RTOG) guidelines proposed in 2013. The central points of the metastatic lymph nodes of the PLV region in the patients were recreated proportionally on the CT images of a standard patient with N0 NPC in reference to the normal anatomy of the PLV area. The correlation between the PLV region and the other levels, the nodal location, and the characteristics and prognosis of the PLV region were analyzed.Results:Lymph node metastasis occurred in 557 (92.06%) of 605 patients, and the top four areas with the highest probability of metastasis were level IIb (77.85%), level VIIa (73.05%), level IIa (60.0%), and level III (41.48%). There were 30 patients (4.95%) with lymph node metastasis in the PLV region. A total of 49 metastatic lymph nodes from the PLV region were counted, and the mean distance of the central point of each lymph node from the leading edge of the trapezius muscle was 14 mm. Linear regression correlation analysis suggested that lymph node metastasis in the PLV region was associated with ipsilateral level IVa (P=0.018), level Va, level Vb, and level Vc lymph node metastasis (all P<0.001). The 5-year OS, PFS, LRFS, and DMFS of 29 patients with lymph node metastasis in the PLV region were 41.6%, 27.7%, 89.1%, and 47.3%, respectively. The 5-year OS, PFS, LRFS, and DMFS of patients with N3 NPC with or without lymph node metastasis in the PLV region were 41.8% vs 67.3% (P=0.007), 27.8% vs 48.5% (P=0.005), 92.3% vs 80.5% (P=0.521), 40.6% vs 78.4% (P<0.001), respectively. Multivariate analysis showed that lymph node metastasis in the PLV region was an independent prognostic factor for DMFS (P<0.05).Conclusion:NPC patients with lymph node metastasis in the PLV region had a poor prognosis and a high risk of distant metastasis. When patients have lymph node metastasis in levels IVa and V, the posterior boundary of the radiotherapy target in ipsilateral level V should be appropriately moved backward. We recommend that the margin of the PLV region may be a new cervical lymph node segment for head and neck tumors.

scholarly journals Distribution pattern and prognosis of metastatic lymph nodes in cervical posterior to level V in nasopharyngeal carcinoma patients

2020 ◽  
Author(s):  
Chaoyang Jiang ◽  
Hui Gao ◽  
Ling Zhang ◽  
Hua Li ◽  
Tao Zhang ◽  
...  
Keyword(s):  
Lymph Node ◽  
Nasopharyngeal Carcinoma ◽  
Lymph Node Metastasis ◽  
Lymph Nodes ◽  
Distribution Pattern ◽  
Cervical Region ◽  
Target Area ◽  
Metastatic Lymph Nodes ◽  
Node Metastasis ◽  
Metastatic Lymph

Abstract Background:Lymph node metastasis in the cervical region posterior to level V (PLV) can occurs in patients with nasopharyngeal carcinoma (NPC), but the significance of lymph node metastasis in this region and the delineation of the radiotherapy target area have not been reported. We aimed to explore the distribution pattern and prognosis of metastatic lymph nodes in the PLV region in patients with NPC.Methods:We retrospectively studied 605 cases of NPC diagnosed by pathological detection from December 2011 to November 2017. All patients were subjected to an enhanced CT scan from the cranial apex to 2 cm below the sternoclavicular joints. The nodal distribution at each level was assessed in accordance with the Radiation Therapy Oncology Group (RTOG) guidelines proposed in 2013. The central points of the metastatic lymph nodes of the PLV region in the patients were recreated proportionally on the CT images of a standard patient with N0 NPC in reference to the normal anatomy of the PLV area. The correlation between the PLV region and the other levels, the nodal location, and the characteristics and prognosis of the PLV region were analyzed.Results:Lymph node metastasis occurred in 557 (92.06%) of 605 patients, and the top four areas with the highest probability of metastasis were level IIb (77.85%), level VIIa (73.05%), level IIa (60.0%), and level III (41.48%). There were 30 patients (4.95%) with lymph node metastasis in the PLV region. A total of 49 metastatic lymph nodes from the PLV region were counted, and the mean vertical distance of the central point of each lymph node from the anterior surface of the trapezius muscle was 14 mm. Linear regression correlation analysis suggested that lymph node metastasis in the PLV region was associated with ipsilateral level IVa (P=0.018), level Va, level Vb, and level Vc lymph node metastasis (all P<0.001). The 5-year OS, PFS, LRFS, and DMFS of 29 patients with lymph node metastasis in the PLV region were 41.6%, 27.7%, 89.1%, and 47.3%, respectively. The 5-year OS, PFS, LRFS, and DMFS of patients with N3 NPC with or without lymph node metastasis in the PLV region were 41.8% vs 67.3% (P=0.007), 27.8% vs 48.5% (P=0.005), 92.3% vs 80.5% (P=0.521), 40.6% vs 78.4% (P<0.001), respectively. Multivariate analysis showed that lymph node metastasis in the PLV region was an independent prognostic factor for DMFS (P<0.05).Conclusion:NPC patients with lymph node metastasis in the PLV region had a poor prognosis and a high risk of distant metastasis. We recommend that the margin of the PLV region may be a new cervical lymph node segment for NPC.

scholarly journals Distribution pattern and prognosis of metastatic lymph nodes in cervical posterior to level V in nasopharyngeal carcinoma patients

2020 ◽  
Author(s):  
Chaoyang Jiang ◽  
Hui Gao ◽  
Ling Zhang ◽  
Hua Li ◽  
Tao Zhang ◽  
...  
Keyword(s):  
Lymph Node ◽  
Nasopharyngeal Carcinoma ◽  
Lymph Node Metastasis ◽  
Lymph Nodes ◽  
Cervical Region ◽  
Target Area ◽  
Metastatic Lymph Nodes ◽  
Node Metastasis ◽  
Neck Tumors ◽  
Metastatic Lymph

Abstract Lymph node metastasis in the cervical region posterior to level V (PLV) often occurs in patients with nasopharyngeal carcinoma (NPC), but the significance and the delineation of the radiotherapy target area have not been reported. We retrospectively studied 605 cases of NPC. A total of 49 metastatic lymph nodes from the PLV region were counted. Linear regression correlation analysis suggested that lymph node metastasis in the PLV region was associated with ipsilateral level IVa, level Va, level Vb, and level Vc lymph node metastasis (all P<0.05). The 5-year OS, PFS, LRFS, and DMFS of patients with N3 NPC with or without lymph node metastasis in the PLV region were 41.8% vs 67.3% (P=0.007), 27.8% vs 48.5% (P=0.005), 92.3% vs 80.5% (P=0.521), 40.6% vs 78.4% (P<0.001), respectively. Multivariate analysis showed that lymph node metastasis in the PLV region was an independent prognostic factor for DMFS (P<0.05). In summary, NPC patients with lymph node metastasis in the PLV region had a poor prognosis and a high risk of distant metastasis. When patients have lymph node metastasis in levels IVa and V, the posterior boundary of the radiotherapy target in ipsilateral level V should be appropriately moved backward. We recommend that the margin of the PLV region may be a new cervical lymph node segment for head and neck tumors.

scholarly journals Lymph node metastasis in the space between the right carotid artery and jugular vein in papillary thyroid carcinoma

2020 ◽  
Vol 48 (4) ◽  
pp. 030006052092003
Author(s):  
Jian Chen ◽  
Deguang Zhang ◽  
Liang Fang ◽  
Gaofei He ◽  
Li Gao
Keyword(s):  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Lymph Nodes ◽  
Papillary Thyroid ◽  
Thoracic Inlet ◽  
Primary Tumor Size ◽  
Metastatic Lymph Nodes ◽  
Node Metastasis ◽  
Metastatic Lymph ◽  
The Right

Background The oblique brachiocephalic trunk and right common carotid artery constitute the right carotid sheath space (RCSS). The aim of this study was to detect the clinicopathologic factors associated with RCSS lymph node metastasis. Methods In total, 232 papillary thyroid carcinoma (PTC) patients with preoperative contrast-enhanced computed tomography scans were analyzed for associations between RCSS lymph node metastasis and clinicopathological factors. Results Among the 232 cases, 18 (7.76%) had suspicious RCSS lymph nodes, which was correlated with the presence of >5 metastatic lymph nodes, a larger thoracic inlet, and primary tumor size >2.15 cm. All pathologically confirmed metastatic lymph nodes were >1 cm in diameter. Conclusions The concept of “RCSS lymph node metastasis” was first introduced by this study. For PTC patients, a larger thoracic inlet, increased number of metastatic lymph nodes, and larger primary tumor size were related to RCSS lymph nodes, and more attention should be paid to patients who have lymph nodes >1 cm. A future prospective study will be designed to identify the potential risk factors for RCSS lymph node metastasis.

scholarly journals A study of the correlation between M2 macrophages and lymph node metastasis of colorectal carcinoma

2021 ◽  
Author(s):  
Yanping Wang ◽  
Jikun Wang ◽  
Chunyu Yang ◽  
Yue Wang ◽  
Jinhao Liu ◽  
...  
Keyword(s):  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Colorectal Carcinoma ◽  
Lymph Nodes ◽  
Comprehensive Treatment ◽  
M2 Macrophage ◽  
M2 Macrophages ◽  
Metastatic Lymph Nodes ◽  
Node Metastasis ◽  
Metastatic Lymph

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.

Loss of ASXL1 protein is associated with lymph node metastasis in colorectal cancer

2019 ◽  
Author(s):  
Jun Ho Lee ◽  
Ju-Hee Lee ◽  
Byung Kyu Ahn ◽  
Seung Sam Paik ◽  
Hyunsung Kim ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Protein Expression ◽  
Lymph Nodes ◽  
Disease Free Survival ◽  
Prognostic Impact ◽  
Metastatic Lymph Nodes ◽  
Node Metastasis ◽  
Metastatic Lymph

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.

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