The link between a lung tumor and the lung microbiome is a largely unexplored issue. To investigate the relationship between a lung microbiome and the phenotype of an inflammatory stromal infiltrate, we studied a cohort of 89 patients with non-small cell lung cancer. The microbiome was analyzed in tumor and adjacent normal tissue by 16S rRNA amplicon sequencing. Characterization of the tumor stroma was done using immunohistochemistry. We demonstrated that the bacterial load was higher in adjacent normal tissue than in a tumor (p = 0.0325) with similar patterns of taxonomic structure and alpha diversity. Lung adenocarcinomas did not differ in their alpha diversity from squamous cell carcinomas, although the content of Gram-positive bacteria increased significantly in the adenocarcinoma group (p = 0.0419). An analysis of an inflammatory infiltrate of tumor stroma showed a correlation of CD68, iNOS and FOXP3 with a histological type of tumor. For the first time we showed that high bacterial load in the tumor combined with increased iNOS expression is a favorable prognostic factor (HR = 0.1824; p = 0.0123), while high bacterial load combined with the increased number of FOXP3+ cells is a marker of poor prognosis (HR = 4.651; p = 0.0116). Thus, we established that bacterial load of the tumor has an opposite prognostic value depending on the status of local antitumor immunity.

Background. Tumor-associated macrophages (TAMs) and tumor-infiltrating lymphocytes (TILs) contribute significantly to the development of immunosuppressive properties of a tumor. In this study, we performed immunohistochemical analysis of immune cells of esophageal tumors stroma. Methods. Paraffin-embedded tissue specimens from 48 esophageal squamous cell carcinoma (ESCC) patients were retrospectively collected for immunohistochemical analysis of stromal cells. For staining of macrophages, CD68, CD163, CD206, PU.1, and iNOS were used. For T cell detection, CD8, CD3, and FOXP3 were used. Also, we performed staining for PD-L1 that can be expressed on TAMs and tumor cells. Clinicopathological and survival data were collected and analyzed using the χ2 and Fisher exact tests, Kaplan–Meier curves, and the log-rank test. The correlation analysis was performed with Spearman’s rank correlation coefficient. Results. We found that FOXP3 expression was associated with age (p=0.042) and iNOS expression was associated with the disease stage (p=0.044). In addition, FOXP3 and CD163 appeared to be markers of good prognosis (HR=0.4420, p=0.0325, and HR=0.4447, p=0.0456, respectively). Significant association between PU.1+ and CD68+ macrophages (r=0.833; p≤0.001) and between PU.1+ and CD163+ macrophages (r=0.500; p≤0.001) was established; positive association between PU.1 and CD206 expression was also observed (r=0.250; p=0.043). Conclusions. Large amounts of CD163+ macrophages and FOXP3+ Т cells appear to be markers of good prognosis of ESCC. The number of PU.1+ macrophages strongly correlates with the number of CD68+ macrophages; therefore, usage of PU.1 as a potential macrophage marker can be recommended for esophageal tumors.

Esophageal cancer is one of the most aggressive malignant neoplasms, with low survival rates and limited treatment options. In this study we analyzed the microbiome composition and the phenotype of inflammatory tumor infiltrate in squamous cell carcinoma of esophagus (ESCC) and examined possible relationships between them and their prognostic significance. We found that the predominant phyla of microorganisms found in both tumors and adjacent normal tissues were Firmicutes, Proteobacteria, Actinobacteria, Gemmatimonadetes and Bacteroidetes. We established that only bacteria of the genus Staphylococcus differ between tumors and normal tissues. We found a significant correlation between bacterial burden and the phenotype of the tumor stroma. Namely, a group of tumors characterized by a high expression of CD206 (r = −0.3976, p = 0.0056) in the stroma and iNOS (r = −0.2953, p = 0.0439) in tumor cells is characterized by a higher bacterial burden. Further, we established that in the group with a high content of CD206+ macrophages, there is also a predominance of gram-positive bacteria over gram-negative ones. We found that gram-positive bacterial burden is associated with disease prognosis in ESCC showing high content of CD206+ macrophages. In conclusion we established that the tumor microbiome, can be prognostically significant for ESCC when combined with other stromal markers.

There is an urgent need for identification of new prognostic markers and therapeutic targets for non-small cell lung cancer (NSCLC). In this study, we evaluated immune cells markers in 100 NSCLC specimens. Immunohistochemical analysis revealed no prognostic value for the markers studied, except CD163 and CD206. At the same time, macrophage markers iNOS and CHID1 were found to be expressed in tumor cells and associated with prognosis. We showed that high iNOS expression is a marker of favorable prognosis for squamous cell lung carcinoma (SCC), and NSCLC in general. Similarly, high CHID1 expression is a marker of good prognosis in adenocarcinoma and in NSCLC in general. Analysis of prognostic significance of a high CHID1/iNOS expression combination showed favorable prognosis with 20 months overall survival of patients from the low CHID1/iNOS expression group. For the first time, we demonstrated that CHID1 can be expressed by NSCLC cells and its high expression is a marker of good prognosis for adenocarcinoma and NSCLC in general. At the same time, high expression of iNOS in tumor cells is a marker of good prognosis in SCC. When used in combination, CHID1 and iNOS show a very good prognostic capacity for NSCLC. We suggest that in the case of lung cancer, tumor-associated macrophages are likely ineffective as a therapeutic target. At the same time, macrophage markers expressed by tumor cells may be considered as targets for anti-tumor therapy or, as in the case of CHID1, as potential anti-tumor agents.

No abstract

Почечно-клеточная карцинома представляет собой гетерогенную группу опухолевых заболеваний, характеризующуюся высокой васкуляризированностью и иммуногенностью. Иммунотерапия совершила прорыв в лечении данной патологии, однако недостаточность выработки критериев ее применения не позволяет добиться еще больших успехов. Известно, что в успехе иммунотерапии немаловажную роль играет опухолевая строма. Среди различных гистологических типов опухолей почки строма светлоклеточного варианта почечно-клеточной карциномы изучена достаточно подробно. Однако остальные гистологические типы практически не изучены. Цель исследования-описание иммуносупрессорного фенотипа стромы опухолей почки различных гистологических типов.

Introduction. Tumor-associated macrophages (TAMs) are traditionally considered to be a pro-tumor fac-tor that promotes the growth of various tumors; however, for colorectal carcinomas (CRC), the prognostic significance of TAMs has not been fully determined, which may be due to the lack of macrophage markers suitable for this tumor type. The aim of this work was to study the expression of the nuclear marker of stromal cells PU.1 in colorectal tumors and its association with the clinical and morphological tumor characteristics. Materials and methods. We performed an immunohistochemical analysis to assess the expression of PU.1, CD68, and CD20 in 85 primary CRCs. The Mann-Whitney test was used to determine statistically significant differences in independent groups. Correlation analysis of the expression of the studied protein was carried out by determining the Spearman’s rank correlation coefficient. Differences were considered statistically significant at p <0.05. Results. We analyzed the expression of PU.1, CD68, and CD20 in CRC and detected positive PU.1 and CD68 expressions in tumor stromal cells in all of the studied samples. Expression of CD20 was observed in 87% of cases. We showed that in colorectal tumors all CD68+ or CD20+ cells express PU.1 and that PU.1 and CD20 were significantly associated with the disease stage (p=0.036 and p=0.002) and the presence or absence of regional metastases (p=0.022 and p=0.007). In addition, PU.1 showed a significant correlation with the distant metastases’ presence and tumor localization (p=0.031 and p=0.022). Higher content of PU.1 was typical for colon tumors without metastases. CD20 also showed a significant association with tumor size (p=0.025). No significant correlations with clinical and morphological features were found for CD68. We also demonstrated that the number of PU.1+ cells in tumors significantly positively correlates with CD68 (r=0.231, p=0.036) and CD20 (r=0.267, p=0.015). Conclusion. The results of this study indicate that PU.1 can be considered as an independent marker of a favorable prognosis in CRC patients. Keywords: colorectal cancer, expression, CD20, CD68, PU.1, macrophages, B-cells

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.