Abstract
Substantial evidence indicates that gastric microbiota dysbiosis, immune system dysfunction especially immune escape are critical for gastric cancer (GC) occurrence and progression. As two important elements of tumor microenvironment (TME), the relationship between gastric microbiota and tumor-immune microenvironment is still unclear. Our present study aimed to explore the correlation between gastric mucosal microbiota in different microhabitats and its corresponding gastric immunosuppressive cells such as regulatory T cells (Tregs) and plasmacytoid dendritic cells (pDCs) in the TME. A cohort of 64 GC patients without preoperative chemotherapy was enrolled retrospectively, and 60 normal, 61 peritumoral and 59 tumoral tissues were obtained for gastric mucosal microbiota analysis and immunohistochemistry analysis. From different microhabitats, BDCA2+pDCs and Foxp3+Tregs were observed positively correlated, and increased in tumoral and peritumoral tissues compared to normal ones. The diversity, composition and function of gastric mucosal microbiota also changed more significantly in tumoral tissues than those in normal and peritumoral ones. With pearson's correlation analysis, we found that several non-abundant genera such as Stenotrophomonas and Selenomonas were positively correlated with BDCA2+pDCs and Foxp3+Tregs, respectively, while Comamonas and Gaiella were negatively correlated with BDCA2+pDCs and Foxp3+ Tregs, respectively. The increased BDCA2+pDCs and Foxp3+Tregs might be modulated by gastric mucosal microbiota, both participated in the immunosuppression microenvironment of GC, which might provide evidence to establish new strategies in antitumor therapy targeting on gastric microbiota.
Highlights
Gastric cancer (GC) is a major health problem causing significant morbidity and mortality, ranking the third most common cause of cancer-related mortality worldwide [1, 2]
Immunohistochemical staining of Blood dendritic cell antigen-2 (BDCA2) revealed that the absolute numbers of plasmacytoid dendritic cells (pDCs) were present in stomach peritumoral and tumoral tissues of gastric cancer (GC) patients, and Foxp3 indicated that Tregs were increased than those in normal tissues (Figure 1A)
We found that the numbers of BDCA2+pDCs in tumoral tissues were significantly lower than that in peritumoral tissues (p < 0.05)
Summary
Gastric cancer (GC) is a major health problem causing significant morbidity and mortality, ranking the third most common cause of cancer-related mortality worldwide [1, 2]. Over the past decades, increasing evidence indicates that the pathogenetic mechanisms of cancer encompass tumor microenvironment (TME), emphasizing a tight correlation with its alterations for cancer initiation, progression and metastasis. The immune surveillance is considered to be an important host protection process to inhibit carcinogenesis and to maintain cellular homeostasis, while evading immune surveillance is a hallmark of biological capabilities in cancer development [3]. The TME immune suppression is of the upmost importance for tumor cell survival, invasiveness and metastatic dissemination. New strategies for overcoming TEM immune suppression have led to the new and innovative cancer therapies that are considered amongst the medical breakthroughs
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