Introduction, mechanism and application of necroptosis in tumor immunity

Cell death can be divided into two modes: regulatory cell death (RCD) and accidental cell death (ACD)

Necroptosis combines the characteristics of both (necrosis and apoptosis), during which morphological changes such as organelle swelling, cell membrane rupture, and cytoplasmic and nuclear disintegration can be observed.

Figure 1.

On August 21, 2021, You-Sun Kim's team from South Korea published a research paper titled RIPK3 activation induces TRIM28 derepression in cancer cells and enhances the anti-tumor microenvironment in Molecular Cancer, using TAP-MS Methods, combined with analysis of RNA sequencing (RNA-Seq) datasets, identified TRIM28 as a co-repressor that regulates transcriptional activity during necroptosis

Figure 2.

On May 25, 2022, another new discovery about necroptosis was made in the field of tumor immunity

CBL0137 triggers the formation of L-Z-DNA in cells and activates the ZBP1-dependent necroptosis pathway in cancer-associated fibroblasts

Figure 3.

CBL0137 activates ZBP1-dependent nuclear necroptosis: triggers the response between ZBP1, RIPK3 and MLKL by inducing Z-DNA accumulation

A key challenge in the detection of necroptosis is to distinguish it from apoptosis and necrosis

■ Morphological changes

The morphological change of cell death is a dynamic process, therefore, the entire process needs to be "monitored" in real time to confirm the occurrence of necroptosis

■ Inhibition and knockout

Necroptosis inhibitors, RIPK1 inhibitor Necrostatin-1 and MLKL inhibitor Necrosulfonamide, were used to block necroptosis, measure cell viability, and reversely verify the occurrence of necroptosis

■ Key protein detection

Changes in key proteins in the necroptosis pathway such as RIPK3, RIPK1 and MLKL were detected by Western blot, immunohistochemistry or flow cytometry

Figure 4.

■ Key protein detection

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Vaccination with Necroptotic Cancer Cells Induces Efficient Anti-tumor Immunity.
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Baik JY, Wan P, Liu ZG.
Examining MLKL phosphorylation to detect necroptosis in murine mammary tumors.
STAR Protoc.
2022 Jun 14;3(3):101457.