Microbiota and microbial metabolites initiate antitumor immune responses by inducing ICD. (IMAGE)
Caption
Microbiota and microbial metabolites initiate antitumor immune responses by inducing ICD. This schematic systematically illustrates the complete process by which microbiota and microbial metabolites, serving as inducers of ICD, ultimately initiate specific antitumor immune responses through a cascade of “ICD induction–DAMPs release–DAMPs recognition–DC maturation–antigen presentation–T cell activation and tumor killing.” 1. ICD induction: Microbiota and microbial metabolites act on tumor cells as inducers of ICD, triggering ICD in tumor cells. 2. DAMPs release: Dying tumor cells undergoing ICD release or expose various DAMPs, including ATP, HMGB1, and HSPs, as well as the translocation of CRT from the ER to the cell surface. 3. DAMPs recognition: The released DAMPs are recognized and taken up by immature DCs and these DAMPs initiate the activation program of the DCs. 4. DC maturation: Stimulated by DAMPs, immature DCs differentiate into mature DCs. This transition equips DCs with a highly efficient antigen-presenting capacity. 5. Antigen presentation: Mature DCs present tumor antigens via MHC molecules on the surface to the TCRs on CD8+ T cells, thereby establishing a bridge for antigen-specific recognition. 6. T cell activation and tumor killing: CD8+ T cells that recognize the antigen–MHC complex are activated, initiating a specific antitumor immune response. These activated CD8+ T cells (effector T cells) can precisely recognize and kill tumor cells. ATP, adenosine triphosphate; CRT, calreticulin; DAMPs, damage-associated molecular patterns; DC, dendritic cell; ER, endoplasmic reticulum; HMGB1, high mobility group box 1; HSPs, heat shock proteins; ICD, immunogenic cell death; MHC, major histocompatibility complex; TCR, T cell receptor.
Credit
Cancer Biology & Medicine
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