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Growing evidence implicates that intratumoral microbiota are closely linked to cancer progression; however, research on the role of these microbiota in the development of gastric cancer remains limited. Here, using 16 S rRNA sequencing, tumor tissue proteomics and serum cytokines analysis, we identified enrichment of specific microbial communities within tumors of gastric cancer patients, possibly affecting the tumor microenvironment by immune modulation, metabolic processes, and inflammatory responses. Based on the results of in vivo experiments and intratumoral microbiota analysis, we found that Streptococcus mitis can inhibit gastric cancer progression via suppressing M2 macrophage polarization and infiltration, as well as altering the intratumoral microbial community. In summary, our findings suggest that the intratumoral microbiota, exemplified by Streptococcus mites, may be involved in regulating the progression of gastric cancer, thereby emerging as potential therapeutic targets for this disease. [ABSTRACT FROM AUTHOR]

Introduction Mutations of the KRAS gene are the most common drivers of tumor development across a spectrum of human cancers, such as cancers of the lung, colon, and pancreas (1-3). [...], KRAS is one of the most frequently activated oncogenes in human cancers. Although the role of KRAS mutation in tumorigenesis and tumor maintenance has been extensively studied, the relationship between KRAS and the tumor immune microenvironment is not fully understood. Here, we identified a role of KRAS in driving tumor evasion from innate immune surveillance. In samples of lung adenocarcinoma from patients and Kras- driven genetic mouse models of lung cancer, mutant KRAS activated the expression of cluster of differentiation 47 (CD47), an antiphagocytic signal in cancer cells, leading to decreased phagocytosis of cancer cells by macrophages. Mechanistically, mutant KRAS activated PI3K/STAT3 signaling, which restrained miR-34a expression and relieved the posttranscriptional repression of miR-34a on CD47. In 3 independent cohorts of patients with lung cancer, the KRAS mutation status positively correlated with CD47 expression. Therapeutically, disruption of the KRAS/CD47 signaling axis with KRAS siRNA, the [KRAS.sup.G12C] inhibitor AMG 510, or a miR-34a mimic suppressed CD47 expression, enhanced the phagocytic capacity of macrophages, and restored innate immune surveillance. Our results reveal a direct mechanistic link between active KRAS and innate immune evasion and identify CD47 as a major effector underlying the KRAS-mediated immunosuppressive tumor microenvironment.