Objectives. Among various cells of tumor immune microenvironment (TIME) macrophages have been shown to play a pivotal role in the prognosis of many malignancies including laryngeal squamous cell carcinoma (LSCC). Laryngopharyngeal reflux (LPR) is associated with LSCC and can impact its prognosis. Local factors, particularly pH, can affect cancer growth by altering TIME and tumor associated macrophages phenotype. However, it is still unknown whether and how LPR affects TIME and macrophages polarization in LSCC. In this study we compared macrophage polarization in LSCC of patients with and without coexisting LPR.Methods. A total of 63 patients with T1-2 LSCC without (the 1st group, 30 patients) and with coexisting LPR (the 2nd group, 33 patients) were enrolled in the study. Only HPV-negative cases of males were included in the study. Immunohistochemistry was performed to visualize CD68 and CD163 macrophages. The number of macrophages was counted at the central tumor clusters (TC), peritumor stroma (TS) and at the intact laryngeal mucosa (IM) taken from the tumor-negative edge. Results. Samples of the 2nd group patients with LSCC and LPR demonstrated significantly (P<0.05) higher inflammatory infiltration of all the evaluated compartments (TC, TS and IM). CD68+ cells count was comparable in TC and IM of the 1st and the 2nd group patients. In contrast, CD163+ cells were more numerous in the 2nd group patients in TC, TS and IM (P<0.001). Moreover, the number of M2 macrophages was significantly higher than M1 macrophages in patients with coexisting LPR. As a result, CD163/CD68 ratio was significantly (P<0.001) higher in LSCC with coexisting LPR.Conclusions. LPR is associated with altered macrophages polarization and increase of M2-type macrophages in LSCC. The shift in macrophage polarization towards the M2 type in patients with LPR could facilitate LSCC development and progression.
Western blots demonstrated decreased levels of ZFP161 protein in Zfp161 knockout and shRNA knockdown cells. Simultaneously, decreased c-MYC protein levels were observed in Zfp161 knockout and shRNA knockdown cells compared with wild type and knockdown control cells. Using qPCR, decreased c-Myc RNA levels were observed in Zfp161 knockout cells compared to wildtype cells and decreased c-Myc RNA levels were observed in shRNA knockdown cells compared to control cells. Our results show that knockout and knowdown of Zfp161 results in a significant decrease in c-Myc expression in human cells. The decrease of c-Myc in Zfp161 knockout and knockdown cells translated into a robust decrease of in vitro cell survival in colony formation assays.Conclusions: Zfp161 is a regulator of the c-Myc oncogene in human cells. Zfp161 knockout and knowdown cells show a robust decrease of cell survival in vitro.
The purpose of this study was to evaluate the effect of the laryngopharyngeal reflux (LPR) on the number of tumourinfiltrating T-lymphocytes in laryngeal cancer (LC). According to the results of pH monitoring, 87 patients with laryngeal tumours were subdivided into three groups: 1st group included patients with LC without LPR; 2nd group comprised LC patients with coexisting LPR, patients with benign neoplasms of the larynx with LPR were enrolled into 3d group. TIME was assessed immunohistochemically by counting T-lymphocytes (CD3+), T-cytotoxic cells (CD8+) and T-regulatory cells (Treg; FOXP3+) number within the tumour, in the peritumour stroma, and in the intact areas of the larynx. It was shown that LPR leads to chronic inflammation and affects TIME of laryngeal carcinomas. LC with coexisting LPR demonstrated a higher inflammatory infiltration of tumour area and intact mucosa. However, no statistically significant differences were found between a number of CD3+- and CD8+-cells in LC of the 1st and 2nd groups. In contrast, LPR was associated with higher number of immunosuppressive Treg-cells within tumour and in intact mucosa that could affect immune tolerance and efficacy of anti-tumour immunity facilitating LC progression.
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