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Tumor immune escape 🔎
➡️ P2X7R is expressed in most solid and haematological cancer.
📌 P2X7R:
1. Promotes proliferation.
2. Promotes metabolism.
3. Facilitates tumor invasion and metastatic dissemination.
📝 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.
📄 Reference: https://doi.org/10.3389%2Ffimmu.2023.1287310
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