Environmental factors and genetic mutation have caused cancer incidence and mortality to rapidly increase. Cancer has become one of the crucial causes of death worldwide, and is becoming a major public health problem. 1 The traditional core types of cancer treatment are surgery, chemo-therapy, and radiation therapy, which can reduce tumor cell proliferation by inducing cancer cell death. 2 However, accumulating evidence has shown that tumors often relapse and it has been suggested that successful oncotherapy requires prolonged antineoplastic immunity. 3 The field of cancer immunotherapy (CIT) has emerged in recent years and aims to stimulate the body's immune system to create a robust immune response that can kill cancer cells. 4 This type of treatment can induce immunogenic cell death in different ways and achieve long-term anticancer immunity. 5 Although the application of CIT has been considered for a broad range of tumors, only a minority of patients achieve a satisfactory treatment effect due to immune escape. These results indicate that the immune system is intricate and still not well managed. 6 Thus, it is necessary to explore the mechanisms involved in CIT to develop more efficient methods of treatment for better cancer prevention and treatment.

Cysteinyl aspartate specific proteinase (Caspase)‐8 has long been considered a promoter of apoptosis and part of the mechanism by which cytotoxic drugs kill cancer cells. With the continuous exploration of the types of programmed cell death, an increasing number of studies have confirmed that caspase‐8 plays an important role in cancer. Recently, scholars have proposed the term “PANoptosis,” which mainly includes three programmed cell death modes, namely pyroptosis, apoptosis and necroptosis. In addition to mediating endogenous apoptotic pathways, caspase‐8 can also participate in the cleavage of gasdermin (GSDM) family proteins to induce pyroptosis. Furthermore, the expression of enzymatically inactive caspase‐8 (C362S) can cause embryonic lethality and inflammatory tissue destruction in mice by inducing necroptosis and pyroptosis. Therefore, the activation and deletion of caspase‐8 enzyme activity, as well as the knockout of the coding gene, are closely related to “PANoptosis.” In addition, caspase‐8 can also improve the tumor microenvironment and enhance tumor antiimmunity. Studies have shown that caspase‐8 is also associated with tumor growth and invasion, angiogenesis and metastasis, therapeutic resistance and poor clinical outcomes. Therefore, it is very important to measure the cancer‐promoting and anticancer effects of caspase‐8 and find a balance, and to study its role in the effect of “PANoptosis” in depth. This article reviews the role of caspase‐8 in “PANoptosis” in cancer to provide new strategies and targets for cancer.

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The green tea catechin epigallocatechin gallate (EGCG) exhibits antiviral activity against various viruses. Whether EGCG also inhibits the infectivity of circovirus remains unclear. In this study, we demonstrated the antiviral effect of EGCG on porcine circovirus type 2 (PCV2). EGCG targets PCV2 virions directly and blocks the attachment of virions to host cells. The microscale thermophoresis assay showed EGCG could interact with PCV2 capsid protein in vitro with considerable affinity (Kd = 98.03 ± 4.76 μM), thereby interfering with the binding of the capsid to the cell surface receptor heparan sulfate. The molecular docking analysis of capsid–EGCG interaction identified the key amino acids which formed the binding pocket accommodating EGCG. Amino acids ARG51, ASP70, ARG73 and ASP78 of capsid were found to be critical for maintaining the binding, and the arginine residues were also essential for the electrostatic interaction with heparan sulfate. The rescued mutant viruses also confirm the importance of the key amino acids of the capsid to the antiviral effect of EGCG. Our findings suggest that catechins could act as anti-infective agents against circovirus invasion, as well as provide the basic information for the development and synthesis of structure-based anti-circovirus drugs.