📝 P2X7R showed different roles of anti-tumor response in various preclinical studies.
🥈Two oposite role of P2X7R:
1. Genetic deletion of P2X7R shown adverse effect on tumor infiltrating T cells and promotes tumor growth.
2. Systemic P2X7R antagonism in same tomor model shown positive effect and reduce tumor burden.
💥 Mechanism of P2X7R in detail:
1⃣. Sustained exposure of high concentrations of extracellular ATP, produced in the tumor microenvironment (TME), is recognized by the P2X7R on tumor infiltrating lymphocytes cause the ATP-induced cell death (AICD) and also Expression of ART1 by tumor cells can utilize extracellular NAD+ in TME on tumor-infiltrating lymphocytes (TILs) in trans resulting in NAD-induced cell death (NICD).
2⃣. Modified P2X7R is Expressed by tumor cells with low affinity for AICD and NICD allows them to avoid cell death while still exploiting P2X7R-mediated proliferation and growth signalling.
3⃣. CD38 and CD39 mediated catabolism of extracellular NAD and ATP into ADPR and ADP/AMP respectively,
4⃣. CD73 convert ADPR and ADP/AMP into adenosine. CD73 is frequently overexpressed by tumor cells, resulting in polarization of intratumoural immune cells towards a regulatory phenotype (including Tregs and macrophages) as well as reduced proliferation, cytokine production and cytotoxic function of effector lymphocytes.
📝 P2X7R showed different roles of anti-tumor response in various preclinical studies.
🥈Two oposite role of P2X7R:
1. Genetic deletion of P2X7R shown adverse effect on tumor infiltrating T cells and promotes tumor growth.
2. Systemic P2X7R antagonism in same tomor model shown positive effect and reduce tumor burden.
💥 Mechanism of P2X7R in detail:
1⃣. Sustained exposure of high concentrations of extracellular ATP, produced in the tumor microenvironment (TME), is recognized by the P2X7R on tumor infiltrating lymphocytes cause the ATP-induced cell death (AICD) and also Expression of ART1 by tumor cells can utilize extracellular NAD+ in TME on tumor-infiltrating lymphocytes (TILs) in trans resulting in NAD-induced cell death (NICD).
2⃣. Modified P2X7R is Expressed by tumor cells with low affinity for AICD and NICD allows them to avoid cell death while still exploiting P2X7R-mediated proliferation and growth signalling.
3⃣. CD38 and CD39 mediated catabolism of extracellular NAD and ATP into ADPR and ADP/AMP respectively,
4⃣. CD73 convert ADPR and ADP/AMP into adenosine. CD73 is frequently overexpressed by tumor cells, resulting in polarization of intratumoural immune cells towards a regulatory phenotype (including Tregs and macrophages) as well as reduced proliferation, cytokine production and cytotoxic function of effector lymphocytes.
On February 27th, Durov posted that Channels were becoming a source of unverified information and that the company lacks the ability to check on their veracity. He urged users to be mistrustful of the things shared on Channels, and initially threatened to block the feature in the countries involved for the length of the war, saying that he didn’t want Telegram to be used to aggravate conflict or incite ethnic hatred. He did, however, walk back this plan when it became clear that they had also become a vital communications tool for Ukrainian officials and citizens to help coordinate their resistance and evacuations. Overall, extreme levels of fear in the market seems to have morphed into something more resembling concern. For example, the Cboe Volatility Index fell from its 2022 peak of 36, which it hit Monday, to around 30 on Friday, a sign of easing tensions. Meanwhile, while the price of WTI crude oil slipped from Sunday’s multiyear high $130 of barrel to $109 a pop. Markets have been expecting heavy restrictions on Russian oil, some of which the U.S. has already imposed, and that would reduce the global supply and bring about even more burdensome inflation. In the United States, Telegram's lower public profile has helped it mostly avoid high level scrutiny from Congress, but it has not gone unnoticed. Emerson Brooking, a disinformation expert at the Atlantic Council's Digital Forensic Research Lab, said: "Back in the Wild West period of content moderation, like 2014 or 2015, maybe they could have gotten away with it, but it stands in marked contrast with how other companies run themselves today." What distinguishes the app from competitors is its use of what's known as channels: Public or private feeds of photos and videos that can be set up by one person or an organization. The channels have become popular with on-the-ground journalists, aid workers and Ukrainian President Volodymyr Zelenskyy, who broadcasts on a Telegram channel. The channels can be followed by an unlimited number of people. Unlike Facebook, Twitter and other popular social networks, there is no advertising on Telegram and the flow of information is not driven by an algorithm.
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