A GATA4-regulated secretory program suppresses tumors through recruitment of cytotoxic CD8 T cells

The GATA4 transcription factor acts as a master regulator of development of multiple tissues. GATA4 also acts in a distinct capacity to control a stress-inducible pro-inflammatory secretory program that is associated with senescence, a potent tumor suppression mechanism, but also operates in non-senescent contexts such as tumorigenesis. This secretory pathway is composed of chemokines, cytokines, growth factors, and proteases. Since GATA4 is deleted or epigenetically silenced in cancer, here we examine the role of GATA4 in tumorigenesis in mouse models through both loss-of-function and overexpression experiments. We find that GATA4 promotes non-cell autonomous tumor suppression in multiple model systems. Mechanistically, we show that Gata4-dependent tumor suppression requires cytotoxic CD8 T cells and partially requires the secreted chemokine CCL2. Analysis of transcriptome data in human tumors reveals reduced lymphocyte infiltration in GATA4-deficient tumors, consistent with our murine data. Notably, activation of the GATA4-dependent secretory program combined with an anti-PD-1 antibody robustly abrogates tumor growth in vivo.

The role of senescence-associated secretory phenotype (SASP) in cellular senescene

Cellular senescence is one of the defense mechanisms of cells against oncogenic signals by permanently stopping the proliferation of the cell. Senescence cells show a similar characteristic, one of them is senescence-associated secretory phenotype (SASP). SASPs secrete various components, divided according to the type of molecule secreted and based on their mechanism of action against target cells. The main components of SASP are pro-inflammatory mediators. SASP performs dual and contradictory roles, which concurrently provides beneficial effects such as tumor suppression due to the termination of proliferation, recruitment of immune cells, and tissue repair. On the other hand, SASP produces detrimental effects on cells undergoing the senescence process as well as cells in the surrounding environment by increasing tumorigenesis. This review article explains the various components of the SASP, the role of SASP in the inflammatory process, tumor suppression, and tumorigenesis.

Anti-tumor effect of polysaccharide from Pleurotus ostreatus on H22 mouse Hepatoma ascites in-vivo and hepatocellular carcinoma in-vitro model

Hepatocellular carcinoma is one of the leading causes of cancer-associated death across the globe. Malignant ascites are the major clinical attributes in cancer patients. Despite the advancements in HCC treatments such as chemotherapy, radiotherapy, surgery, and hormonal therapy, researchers are pursuing novel natural edible compounds for the treatment of cancer to eliminate dreadful side effects. Pleurotus ostreatus is one of the most edible cuisines in Asia as well as all over the world. It has been a source of nutritious diet since it was classified as an edible mushroom with no or negligible side effects. The present study focused on the natural anti-cancerous and anti-ascites capabilities of polysaccharides extracted from Pleurotus ostreatus in-vivo as well as in-vitro. Administration of polysaccharide Pleurotus ostreatus showed a significant decrease in tumor cell metastasis while the increase in the survival period among mice models of H22 malignant ascites. Downregulation of regenerative genes Foxp3 and Stat3 and secretion of immunological factors such as IL-2, TNF α, and INF γ were observed after treating with the partially pure extracted polysaccharide. Twining with the hypothesis of tumor suppression in-vivo model polysaccharide showed a decrease in invasion and migration abilities and henceforth responsible for the gene regulation such Cytochrome C which supposedly induced the chain of gene regulation process resulting in apoptosis in HCC cell lines observed in-vitro experiments. Collective research findings manifested that polysaccharide extracted from Pleurotus ostreatus bears anti-proliferative activity and thus influence tumor suppression in-vivo and in-vitro against hepatocellular carcinoma and can be used for therapeutic purposes as a potential anti-cancerous source in the future.