It's not just the immuno-checkpoint Nature sub-journal that reveals the new mechanism of PD-L1 in tumor coke death.

Caspase-1, -4, -5 or -11 cutting Gasdermin D (GSDMD) is a typical coke path.
Recent studies have shown that selective delivery of active Gasdermin proteins to cancer cells or particle-enzyme-oriented cutting of Gasdermin B (GSDMB) and GSDME in cancer cells can induce strong anti-tumor immunity, suggesting that we can induce tumor cell coke death for cancer treatment.
September 14, 2020, the Mien-Chie Hung task force at the Anderson Cancer Center at the University of Texas presented a paper entitled PD-L1-mediated gasdermin C expression switches at Nature Biology Apoptosis topyroptosis in cancer cells and helpers tumour necrosis, the first study to find nPD-L1 / GSDMC / caspase-8 mediated cancer cell coke death, resulting in tumor necrosis.
DOI:10.1038/s41556-020-0575-z To study the physiological effects of nPD-L1, the researchers screened stimulants that may affect nPD-L1 expression levels in MDA-MB-231 cells, including stress, autophagy, cytokines, clinical drugs, and PD-L1 antibodies.
results show that 72 hours of low oxygen treatment can induce a large number of PD-L1 molecules into the nucleus.
, the researchers tested whether there was an interaction between p-Y705-Stat3 and PD-L1 in MDA-MB-231 cells.
found that p-Y705-Stat3 had a physical interaction with PD-L1, and that the interaction required the involvement of the in-cell domain of PD-L1.
, PD-L1's nuclear susceptible was significantly impaired in cells stablely expressed by Stat3-Y705F mutants.
although PD-L1 and p-Y705-Stat3 bind to each other in cytoplocytes, treatment with importin alpha and beta inhibitor ivesin inhibits PD-L1 nuclear translocation.
PD-L1/P-Y705-Stat3 interactions in MDA-MB-231 cells Next, the researchers found that cell coke death occurred in a variety of cancer cells, including lung, breast, liver and ovarian, and melanoma, and that Stat3, which inhibits phosphorylation, was effective in preventing PD-L1 from entering the nucleus.
, nPD-L1 switches TNF alpha-induced coke death to coking phosphate in tumor cells under hypoxia.
PD-L1/P-Y705-Stat3 interactions in MDA-MB-231 cells Next, the researchers found that cell coke death occurred in a variety of cancer cells, including lung, breast, liver and ovarian, and melanoma, and that Stat3, which inhibits phosphorylation, was effective in preventing PD-L1 from entering the nucleus.
, nPD-L1 switches TNF alpha-induced coke death to coking phosphate in tumor cells under hypoxia.
Caspase-8 cutting GSDMC induced cell coke death Finally, in vivo experiments showed that inhibiting the nuclear PD-L1-mediated cell coke death path path can significantly alleviate tumor necrosis symptoms and prolong the survival of lotus mice.
researchers also found that antibiotic-based chemotherapy drugs can induce the expression of nPD-L1 and GSDMC, as well as the activation of caspase-8, leading to the death of cancer cells, affecting the anti-tumor immunity and prognosis of patients with PD-L1 plus or GSDMC plus cancer.
GSDMC, nPD-L1, and caspase-8 are necessary for tumor necrogation in hypoxia-deprived areas caused by TNF alpha Until now, most PD-L1 studies have focused on the function of their immune checkpoints.
the study sheds light on the need for nPD-L1, caspase-8, and GSDMC for tumor necrosis, revealing a path path path that is very different from the coke death of macrophages.
also suggested that antibiotic chemotherapy drugs can enhance anti-tumor immunity in the treatment of PD-L1 plus or GSDMC plus breast tumors, which provides an important reference for subsequent tumor treatment.
resources: pD-L1-mediated gasdermin C expression switches apoptosis to pyroptosis in cancer cells and helpers tumour necrosis.