Immunosuppressive Phenotype of Esophagus Tumors Stroma

Abstract

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.

ANXA1 (Annexin A1) regulated by MYC (MYC proto-oncogene) promotes the growth of papillary thyroid carcinoma

“…In recent studies, some people find ANXA1 is related to T cells in PTC, which is similar to our results [ 22 ]. T cells regulatory suppress immune activity in cancer, unlike T cells CD8 and ANXA1 expression was positively related with T cells regulatory (Tregs), which suggests ANXA1 may function in PTC by affecting the expression of Tregs [ 23 ]. According to the role of ANXA1 including the ROC (0.807) in PTC, ANXA1 may be a potential marker for diagnosing PTC and a potential target for curing PTC.…”

Prognostic significance of CD204 and IDO1 expression in esophageal tumors

“…Для рака пищевода прогностическая роль количества и фенотипа макрофагов, ассоциированных с опухолью, остается противоречивой. Ранее мы показали, что в случае данной нозологии высокое содержание CD163+ макрофагов служит маркером хорошего прогноза, в то время как количество CD206+ макрофагов не является прогностически значимым показателем [17]. Этот факт представляет интерес, поскольку как CD163, так и CD206 являются маркерами макрофагов 2-го типа.…”

Tumor-Associated Macrophages: Combination of Therapies, the Approach to Improve Cancer Treatment

“…Based on observations, TAMs can increase the angiogenesis and metastasis rate in some colorectal cancers [114]. Moreover, macrophages also improve the survival rate in patients suffering from osteosarcoma and esophageal tumors [108,109]. Taking TAM advantages into account, they have also expressed great potential in being diagnostic biomarkers in multiple myeloma, esophageal squamous cell carcinoma, and breast, prostate, bladder, lung, pancreatic and gastric cancers [110][111][112][113].…”