PU.1 is a nuclear factor of immunocompetent cells of tumor stroma in colorectal cancer

Ковалева, О. В.; Gratchev, Alexei; Podlesnaya, P. A.; Рашидова, М. А.; Samoilova, Daria V.; Sokolov, N Yu; Маmedli, Z. Z.; Kudlаy, D.А.; Kushlinskii, N. E.

doi:10.31088/cem2021.10.2.32-39

Cited by 3 publications

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“…Association of its expression with progression of the disease and an unfavorable prognosis were established for both tumor types. PU.1 expression has also been studied in non-small cell lung cancer (NSCLC) [ 13 ], colorectal cancer [ 14 ], and esophageal cancer [ 10 ]. One study was devoted to the study of PU.1 expression in GC, which showed that PU.1 expression is significantly elevated in gastric tumor tissue compared to the relative norm and is associated with an unfavorable prognosis and disease progression.…”

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confidence: 99%

Comprehensive Analysis of Stromal and Serum Markers in Gastric Cancer

et al. 2023

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A comprehensive analysis of the cell phenotype of the inflammatory infiltrate of the tumor stroma represents a promising area of molecular oncology. The study of not only soluble forms of various immunoregulatory molecules, but also their membrane-bound forms is also considered highly relevant. We performed a comprehensive analysis of tissue and circulating forms of the PD-1 and PD-L1 proteins, as well as macrophage and B-cell markers in the tumor stroma of gastric cancer, to assess their clinical and prognostic significance. The tumor and blood plasma samples from 63 gastric cancer patients were studied using ELISA and immunohistochemistry. Malignant gastric tumors were shown to be strongly infiltrated by B-cells, and their number was comparable to that of macrophages. For PU.1 expression, an association with tumor size was observed; i.e., larger tumors were characterized by fewer PU.1+ infiltrating cells (p = 0.005). No clinical significance was found for CD20 and CD163, but their numbers were higher at earlier stages of the disease and in the absence of metastases. It was also demonstrated that the PD-L1 content in tumor cells was not associated with the clinical and morphological characteristics of GC. At the same time, PD-L1 expression in tumor stromal cells was associated with the presence of distant metastases. The analysis of the prognostic significance of all the markers studied demonstrated that CD163 was statistically significantly associated with a poor prognosis for the disease (p = 0.019). In addition, PD-L1 expression in tumor cells tended to indicate a favorable prognosis (p = 0.122). The results obtained in this work indicate that the study of soluble and tissue markers of tumor stroma is promising in prognosticating the course of GC. The search for combinations of markers seems to be highly promising, with their comprehensive analysis capable of helping personalize advanced antitumor therapy.

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Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis of Stromal and Serum Markers in Gastric Cancer

et al. 2023

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Prognostic significance of sPD-1/sPD-L1 in renal cancer depending on the phenotype of tumor and stromal cells

et al. 2022

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Background. The search for new prognostic markers of renal cell carcinoma is an urgent problem of oncourology. Modern studies demonstrate the need for a comprehensive assessment of the clinical and prognostic significance of many markers.Aim is a comprehensive analysis of the prognostic significance of soluble forms of PD-1 and PD-L1 (sPD-1 and sPD-L1) depending on the phenotype of tumor cells and the microenvironment.Materials and methods. The study included tumor tissue and serum samples from 54 patients with renal cell cancer and from 67 healthy donors. The concentrations of sPD-1 and sPD-L1 were determined in blood serum using ELISA. Tissue expression of PD-L1, PU.1, CD3, and CD20 was assessed by immunohistochemistry. To determine statistically significant differences in independent groups, the Mann–Whitney test and Fisher’s exact test were used. Overall survival was analyzed by constructing survival curves using the Kaplan–Meier method. Differences were considered statistically significant at p <0.05.Results. Increase of sPD-L1 concentration in serum from patients with renal cell carcinoma compared with healthy donors was demonstrated. The highest concentration of the soluble form of the PD-1 receptor was observed in serum from patients with the non-clear cell renal cell carcinoma. High levels of sPD-L1 in serum and PD-L1 in tumor cells are associated with disease progression (advanced stage, higher malignancy, as well as the presence of regional metastases). It has been shown that the high content of PU.1+ and CD20+ cells in the tumor stroma are significant factors of unfavorable prognosis. No prognostic significance was found for both sPD-L1 and PD-L1 expressed in tumor tissue. However, analysis of a combination of these markers showed that the high concentration of sPD-L1 together with the high tissue expression of PD-L1 is an extremely unfavorable factor.Conclusion. Analysis of sPD-L1 concentration and tissue expression of PD-L1 in combination is a new approach for assessing the prognosis of renal cell carcinoma.

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Clinical significance of the phenotype of immune cells of the tumor stroma of prostate cancer

et al. 2022

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Introduction. Prostate cancer is by far the most frequently diagnosed cancer among the male population and ranks fifth in the world in terms of mortality rates among malignant neoplasms. Today it is known that the tumor microenvironment plays an important role in the pathogenesis of the disease. Abundant data has accumulated indicating that cells of the inflammatory infiltrate of the tumor are involved in the onset, progression and response to treatment in cases of prostate cancer. However, their role in the context of disease progression has not yet been determined. In this work, we studied the phenotype of inflammatory infiltrate of prostate cancer and its association with the clinical and morphological characteristics of patients.The study objective is to determine the features of the inflammatory infiltrate of prostate cancer and its association with the clinical and morphological characteristics of patients with this disease.Materials and methods. The study included tumor samples obtained from 31 patients with prostate cancer. The expression of CD3, CD8, FoxP3, CD68, PU.1, CD204, CD163, IDO1, PD-L1 (programmed death-ligand 1) was assessed by immunohistochemistry. The relationship between markers and clinical and morphological characteristics was assessed using the nonparametric Mann–Whitney test and Fisher’s exact test. Spearman’s rank correlation coefficient was used to analyze the correlations between contents of cells of different phenotypes. Differences were considered statistically significant at p <0.05.Results. This study describes the features of the stroma of prostate cancer. We have shown that an increased content of CD204+ cells is associated with an older age of patients (p = 0.0026), and the number of CD163+ and CD8+ cells with no metastases to regional lymph nodes (p = 0.0067 and p = 0.0069, respectively). It has been shown that PU.1 can be used as a general marker of macrophages. We also found significant correlations between the level of PU.1 and PD-L1 in the stroma (r = 0.421; p = 0.018) and IDO1 in the stroma (r = 0.557; p = 0.001) and in tumor cells (r = 0.393; p = 0.029), CD68 with IDO1 in the stroma (r = 0.535; p = 0.002), CD163 with PD-L1 and IDO1 in the stroma (r = 0.399; p = 0.026 and r = 0.220; p = 0.026, respectively).Conclusion. In this work, the characteristics of the stroma of prostate cancer were investigated. Our data indicate that tumor associated macrophages are the main cells expressing PD-L1 and IDO1 in the tumor stroma in the case of prostate cancer. Increased expression of IDO1 in tumor tissue is associated with the immunosuppressive phenotype of the inflammatory infiltrate. The fact that the number of macrophages directly correlates with the number of T-lymphocytes in the prostate stroma, and the number of M2 macrophages with cytotoxic T-cells indicates the interaction of the mechanisms of innate and acquired immunity during the progression of prostate cancer.

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PU.1 is a nuclear factor of immunocompetent cells of tumor stroma in colorectal cancer

Cited by 3 publications

References 16 publications

Comprehensive Analysis of Stromal and Serum Markers in Gastric Cancer

Comprehensive Analysis of Stromal and Serum Markers in Gastric Cancer

Prognostic significance of sPD-1/sPD-L1 in renal cancer depending on the phenotype of tumor and stromal cells

Clinical significance of the phenotype of immune cells of the tumor stroma of prostate cancer

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