摘要：SummaryImmunogenic cell death (ICD) in malignant cells can decrease tumor burden and activate antitumor immune response to obtain lasting antitumor immunity, leading to the elimination of distant metastases and prevention of recurrence. Here, we reveal that ppM1 peptide is capable of forming irreparable transmembrane pores on tumor cell membrane, leading to ICD which we name poroptosis. Poroptosis is directly dependent on cell membrane nanopores regardless of the upstream signaling of cell death. ppM1-induced poroptosis was characterized by the sustained release of intracellular LDH. This unique feature is distinct from other well-characterized types of acute necrosis induced by freezing-thawing (F/T) and detergents, which leads to the burst release of intracellular LDH. Our results suggested that steady transmembrane-nanopore-mediated subacute cell death played a vital role in subsequent activated immunity that transforms to an antitumor immune microenvironment. Selectively generating poroptosis in cancer cell could be a promise strategy for cancer therapy.Graphical abstractDisplay OmittedHighlights•ppM1 rapidly aggregates on the plasma membrane to form stable irreparable nanopores•ppM1-formed nanopores induce ICD in tumor cells•Definition of Subacute cell death•ppM1 synergizes PD-1 antibody and therapeutic vaccine in murine tumor modelsCell biology; Functional aspects of cell biology; Cancer
