Table 1.
Summary of pyroptosis inducing mechanisms, cancer models, and impact on adaptive immunity. Arrows indicate the direction in which immune cell levels changed following therapeutic intervention (↑ = increase, ↓ = decrease).
| Agent | Mechanism | Tumor Models | Immune Phenotypes | Citations |
|---|---|---|---|---|
| Oncolytic Viruses (rAAV, HSV-1, VSV, CVB3, ORFV, rMV-Hu191) |
CASP3/GSDME | Various cancer cell lines and models, (e.g., 4T1, EMT6 B16F10, ESCC, CT26) | T cells ↑, NK cells ↑, MDSCs ↓, Tregs ↓, and DC Maturation ↑ | [97,98,99,100,101,102] |
| DNA Damaging Agents (cisplatin, doxorubicin) | CASP3/GSDME | Various cancer cell lines and models, (e.g., 4T1, EMT6 B16F10, GSDME+ HeLa, SH-SY5Y and MeWo cells) | T cells ↑, NK cells ↑, and Macrophage Infiltration ↑ | [31,60,68,69,70,74] |
| BRAFi + MEKi | CASP3/GSDME | BRAF V600E Mut Melanoma | T cells ↑, TAMs ↓, MDSCs ↓ | [67] |
| Cytotoxic Lymphocytes | Granzyme A/GSDMB, Granzyme B/GSDME | GSDME+ or GSDMB+ Cells (EMT6, SH-SY5Y, HeLa, 4T1, SW837, OE19, or SKCO1 cells. CT26,) | Innate Immune recruitment and Activation ↑, Bystander T cells ↑ | [60,62,63,64] |
| Val-boroPro | CARD8, CASP1/GSDMD | Lymphoma, Myeloma, Acute Myeloid Leukemia | DC maturation ↑, Macrophage Activation ↑, T cell recruitment and activation ↑ | [78,79,80,81,82,84] |
| Pan-DPP inhibitor, ARI-4175 | CASP1 | Hepatocellular Carcinoma | T cell Infiltration ↑ | [90] |
| Decitabine + Cisplatin Liposome | CASP3/GSDME | 4T1 Breast Cancer | DC Maturation ↑, CD8+ T cell Infiltration ↑ | [106] |
| NanoCD | CASP3/GSDME | B16F10 Melanoma | T cell Infiltration and co-stimulation ↑, Cytokine Secretion ↑, Tregs ↓, Immunosuppressive CD206+ Macrophages↓ | [107] |
| NP-GSDMA3 | GSDMA3 | 4T1 Breast Cancer | T and NK cell infiltration ↑, M1 Macrophages ↑, Tregs ↓, M2 macrophages↓ | [66] |
| VNP-GD + BAPTA-AM | CASP1/GSDMD + Ca2+ inhibition | 4T1 Breast Cancer, B16F10 Melanoma, Inoperable Ovarian Cancer | DC Maturation ↑, CD8+ T cell infiltration ↑, Cytokine Secretion ↑ | [113] |
| NLRP3 Nanovaccine | NLRP3/CASP1/GSDMD + TLR7/8 agonist | E.G7, B16F10 Melanoma, CT26 Colon Cancer | T cell infiltration ↑, Tregs ↓ | [114] |
| A-C/NP | Photodynamic Trigger, CASP3, GSDME | 4T1 Breast Cancer | T cell activation and infiltration↑ | [120] |
| GSDMB-N LNP | GSDMB | 4T1 breast cancer, B16F10 melanoma | T and NK cell infiltration and activation ↑, DCs maturation and activation ↑, Cytokine secretion ↑ | [65] |
| IL-1β | Released from Canonical Inflammasomes via CASP1/GSDMD | Various models | T cell activation ↑, Dendritic cell maturation ↑ Plasma cell proliferation ↑, MDSC activation ↑, Negative immune feedback ↑, Angiogenesis ↑ | [116,121,122,123,124,125] |
| IL-18 | Released from Canonical and Non-canonical Inflammasomes via CASP1/4/5/GSDMD | Various models | IFNγ producing cells ↑, T and NK cell activation ↑, Angiogenesis↑ | [126,127,128,129,130,131,132,133] |