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

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.

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

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.

The Impact of Metastatic Lymph Node Size on Long-term Outcomes for pStage III Colon Cancer

Aim: To clarify the impact of metastatic lymph node size on long-term outcomes in patients undergoing curative colectomy for pathological stage III colon cancer. Patients and Methods: This study enrolled patients who underwent curative colectomy for pStage III colon cancer between January 2013 and December 2015. All patients were divided into four groups based on the short-axis diameter of the largest MLN: Group A, <5 mm; Group B, ≥5 mm and <10 mm; Group C, ≥10 mm and <15 mm; Group D, ≥15 mm. Results: A total of 209 patients were analyzed. The 5-year recurrence-free survival rates of Groups A, B, C, and D were 82.3%, 74.6%, 74.5% and 60.7%, respectively. In multivariate analysis, Group D (hazard ratio=3.95; 95% confidence interval, 1.34-11.65; p=0.01) was independently associated with worse RFS. Conclusion: Bulky MLNs might be a poor prognostic factor in node-positive colon cancer.

Long-Term Efficacy of Ethanol Ablation as Treatment of Metastatic Lymph Nodes from Papillary Thyroid Carcinoma

Context Ethanol ablation (EA) is considered an alternative to surgery for metastatic lymph nodes from papillary thyroid carcinoma (PTC) in selected patients. Objective The aim of this study was to evaluate the long-term efficacy and safety of this particular treatment. Design and setting Adult patients with PTC who had received EA in lymph node metastasis at a tertiary referral center, and were included in a published study from 2011, were invited to participate in this follow-up study. Methods Radiologic- and medical history were reviewed. Ultrasound examination of the neck was performed by radiologists, and clinical examination was performed by an endocrine surgeon. Response was reported according to predefined criteria for satisfactory EA-treatment. Adverse events associated with EA were evaluated. Cause of death was reported for deceased patients. Results From the 2011-study 51 of 63 patients were included. Forty-four patients were reexamined (67/109 lesions) and 7 patients were deceased. Median follow-up time from primary surgery was 14.5 years. Median follow-up from the latest performed EA in the 2011 study was 11.3 years. Local control was permanently achieved in most patients (80 %). Recurrence within an ablated node was registered in 13 metastases in 10 patients. Seven of these patients also had recurrent disease elsewhere in the neck. No major side effects were reported. Conclusion EA is a minimally invasive procedure with a low risk of complications. Our data suggest that EA is a safe and efficient treatment, providing excellent results for a large group of patients also in the long term.

Postoperative recurrence with right cervical lymph node metastasis in hepatocellular carcinoma: a case report

Background Hepatocellular carcinoma (HCC) patients with metastases to the cervical lymph nodes are extremely rare, and its clinical course is characterized by rapidly progressive disease. Hence, there have been no reports of metastatic cervical lymph node recurrence indicated after a long postoperative surveillance period. Case presentation The patient was a 63-year-old male who underwent right hepatectomy for HCC of the right upper lobe. Three years after resection, metastatic lymph node recurrence was detected in the subdiaphragm, superior mediastinum, and right cervical lymph nodes. The patient underwent excisional biopsy of the cervical lymph node, followed by molecular-targeted therapy and radiation therapy. Lenvatinib reduced the size of all metastatic lymph nodes and the patient survived for a relatively long period of 43 months after the recurrence was detected. Conclusions After resection of HCC in the right upper lobe, there is the possibility of metastatic lymph node recurrence in unusual sites, including the cervical region, and lenvatinib may be effective in those recurrences.

A novel targeted multifunctional nanoplatform for visual chemo-hyperthermia synergy therapy on metastatic lymph nodes via lymphatic delivery

Background Distant metastasis to vital organs is the major contributor to breast cancer mortality, and regional lymph node metastasis is an important facilitator of distant metastasis and recurrence in this cancer. The early diagnosis and precise treatment of lymph node metastasis are crucial for staging and prognosis in breast cancer. Herein, we report a visualized precision medicine nanoplatform of metastatic lymph nodes for ultrasonic/photoacoustic (US/PA) dual modal imaging-guided in situ targeted hyperthermia-combined chemotherapy. Results Carbon nanoparticles (CNs), approved by the China Food and Drug Administration, were loaded with docetaxel and rationally combined with anti-hypoxia-inducible factor 1α antibody-modified poly (lactic-co-glycolic acid) (PLGA) nanoparticles to achieve the combination of passive targeting at the lymph nodes and intracellular targeting at HIF 1α factor. The accumulation and retention of nanoparticles in metastatic lymph nodes via lymphatic delivery were enhanced. Docetaxel could be effectively offloaded by CNs that have active carbon nanoparticles, and the PLGA membrane prevented drug leakage. The nanoparticles exhibited excellent photothermal performance with a photothermal conversion efficiency of 28.9%, killing tumor cells in metastatic lymph nodes through hyperthermia. In vitro and in vivo systematic evaluations revealed that hyperpyrexia triggered the rupture of nanoparticles caused by the phase transition of perfluorohexane, resulting in docetaxel release for achieving in situ hyperthermia-combined chemotherapy. Conclusions The laser-triggered highly efficient in situ chemotherapy nanosystem achieves targeted synergistic chemo-hyperthermia treatment of metastatic lymph nodes, and lymphatic delivery represents a strategy to avoid additional injury caused by drugs entering the blood circulation. Graphical Abstract