Table 1.
Diverse roles of inflammasomes across different cancers
| Cancer Type | Animal Model | In vitro systems |
|---|---|---|
| Lung cancer (implanted tumors) | ■ Rapid growth of LLC cells in mice transduced with human IL-1β–expressing vector54. ■ Decreased lung metastases of B16F10 melanoma, RM-1 prostate, and E0771 mammary adenocarcinoma in Nlrp3−/− mice66. ■ Decreased lung metastases, and tumor growth of B16 melanoma in Il1b−/− mice59 or Il18r−/− mice42. ■ Increased lung metastases of LLC in Casp1−/− Casp11−/− mice63. ■ Reduced tumor growth in nude mice injected with Gsdmd-silenced PC9 cells40. |
■ Decreased proliferation and migration of Nlrp3-silenced, CASP1-inhibited, and IL-18BP–added A549 cells174. ■ Augmentation of IL-1α release from AIM2-activated lung tumor–associated pDCs50. ■ Decreased viability and increased apoptosis in Gsdmd-silenced PC9, H1703, and H1975 cells40. |
| Breast cancer (implanted tumors) | ■ Reduced tumor growth of Py8119 in Il1b−/− mice130. ■ Reduced tumor growth of EO771 or PyT8 or MDA-MB-231 in Casp1−/− and Nlrp3−/− mice65. ■ Reduced tumor growth of MDA-MB-435 in mice treated with AIM2/SN2 DNA108. ■ Reduced tumor progression in 4T1 tumor-bearing mice treated with IL-1R antibody49. ■ Retarded tumor growth in E0771 cells–bearing mice treated with anakinra49. ■ Reduced tumor growth of Py8119 or EO771 cells in diet-induced obese Casp1−/− Casp11−/− or Nlrc4−/− mice130. |
■ Increased migration and invasion of IL-10-treated BT474 cells73. ■ Increased migration of IL-18–treated and decreased migration of Il18-silenced MCF-7 cells 74. ■ Decreased viability and colony-forming ability of Aim2-overexpressed MCF-7, MDA-MB-231, MDA-MB-435, and MDA-MB-453 cells109,108. |
| Fibrosarcoma | ■ Reduced MCA-induced tumor incidence in Nlrp3−/−, Caspl−/− and Il1r−/− mice66. ■ Reduced tumor growth in IL-18-injected mice after implantation of T241 cells175. |
N/A |
| Gastric Cancer | ■ Increased gastric cancer in IL-1B transgenic mice infected with Helicobacter felis33. ■ Reduced gastric preneoplasia in Il1r−/− mice infected with Helicobacter felis176. ■ Reduced tumor volume of Il18-silenced gastric cancer cells in nude mice43. ■ Reduced tumor incidence in gp130F/F Asc−/− or gp130F/F Il18−/− mice32. ■ Decreased tumor growth of Gsdmd-expressing BGC-823 cells in nude mice177. |
■ Suppressed colony formation of AGS and MKN1 cells treated with IL18 neutralizing antibody32. ■ Suppressed colony formation in Asc−/− and Casp1−/− AGS cells32. ■ Decreased proliferation and colony formation in Gsdmd-overexpressed BGC-823 cells and increased proliferation in Gsdmd-silenced BGC-823 cells177. |
| Hepatic Cancer (Implanted tumors) | ■ Regression of CT26 tumors in the liver of WT mice after IL-18 gene transfer178. ■ Decreased hepatic metastases of B16M cells in mice injected with IL-18BP62. ■ Reduced tumor incidence in DEN-treated Casp1−/− and Aim2−/− mice179. ■ Decreased hepatic metastasis of B16 melanoma in Il1b−/− and Casp1−/− Casp11−/− mice58. ■ Increased metastasis in mice injected with Aim2-silenced HCC cells180. ■ Decreased MC38 metastatic tumors in the liver of Nlrp3−/− mice64. ■ Increased MC38 metastatic tumors in the livers of Casp1−/− Casp11−/−, Nlrp3−/−, Il18−/− and Il18r−/− mice63. |
■ Increased migration and invasion of Aim2-silenced HCC cells 180. |
| Colon Cancer (AOM/DSS) | ■ Increased tumors in the colons of Nlrp3−/−78,79, Aim2−/−80,81, Nlrc4−/−82,83, Naip1–6−/−102, Nlrp1b−/−77, Nlrp6−/−83,181,182, Nlrp12−/−115,116, Pyrin−/−84, Asc−/−77–80,83, Casp1−/−78,82, Il18−/−
79,88 and Il18r−/−88 mice. ■ Decreased tumors in colons of IL-18 injected Casp1−/− 79, Pyrin−/−84 or II18−/−84 mice. ■ Decreased tumor in the colons of Casp1−/−183 and Nlrp3R258W mice97. ■ Decreased tumors in the colons of IL-1Ra–injected WT mice184. ■ Increased tumors in the colons of IL-1β–treated complement deficient mice185. ■ More tumors in the colons of Ptpn2r−/− mice treated with a vaccine against IL-1β or in Ptpn2−/− Asc−/− mice98. |
■ Increased proliferation and invasion of HT29, Caco-2, HCA7 and HCT116 cells cocultured with IL-1β–treated normal or cancer-associated fibroblasts186. ■ Decreased survival of AIM2-expressing HCT116 cells104. ■ Decreased migration and invasion of Nlrp3-silenced HCT116, HT29 and SW620 cells76. |
| Prostate Cancer | ■ Decreased metastatic lesions in bones of WT mice injected with Il1b-silenced PC-3 cells and increased metastatic lesions in bones of WT mice injected with IL-1β–overexpressed DU-145 cells187. | ■ Increased migration of IL-1β–stimulated PC-3 cells188. |
| Glioblastoma | ■ Reduced growth of 9L cells in WT mice or WT rats inoculated with BMSCs expressing IL-18189,190 ■ Increased survival and decreased tumor size in WT rats following injection of IL-18-transduced C6 glioma cells191. ■ Decreased tumor size in SR-B10-injected mice followed by administration of recombinant IL-18192. ■ Reduced tumor growth of GL261 and U87 cells in Nlrp3-silenced mice following IR-treatment193. |
■ Increased proliferation, migration and invasion of IL-1β-treated U87 and U251 cells194. ■ Increased apoptosis of IL-1β-treated hypoxic U87 cells195. ■ Decreased viability and increased apoptosis of 9L glioma cells co-cultured with BMSCs expressing IL-18189,190. |
| Skin Cancer Melanoma | ■ Delayed tumor onset in 3-MCA–treated Il1b
−/− mice196. ■ Reduced tumor growth in mice injected with Nlrp1b-silenced 1205Lu cells197. ■ Reduced tumor incidence in DMBA/TPA-treated Il1r−/− and Casp1−/− mice100. ■ Reduced tumor incidence in LysM-Asc−/− mice and increased tumor incidence in K14-Asc−/− mice after DMBA/TPA treatment100. ■ Reduced papilloma lesions in Nlrp3−/− mice198. ■ Increased tumor size in Nlrc4−/− mice challenged with B16F10 cells101. ■ Reduced B16 tumor growth in chimeric WT mice adoptively transferred with Casp1−/− BMCs199. |
■ Increased proliferation of IL-18–treated B16M, A375, HMB2, VUP, SK23, MJM melanoma cells62. ■ Decreased viability and increased apoptosis of Nlrp1b-silenced WM115, 1205Lu and Hs294T cells197. |
| Squamous Cell Carcinoma | ■ Reduced tumor burden in the head and neck of NLRP3 inhibitor (MCC950)-treated Tgfbr1-−/−
Pten−/− mice200. ■ Delayed onset and smaller tumor area in the tongue of 4-NQO–administered and 5-FU–treated Nlrp3−/− and Casp1−/− mice159. ■ Reduced tumor growth in SCID mice injected with Aim2-silenced UT-SCC7 cells39. ■ Reduced tumor growth in nude mice injected with Nlrp3-silenced WSU-HN6 cells69. |
■ More colony formation in LPS+ATP–treated CAL27 cells200. ■ Reduced viability and increased apoptosis of Nlrp3-silenced WSU-HN6 and CAL27 cells treated with 5-FU159. ■ Reduced viability and increased apoptosis of Aim2-silenced UT-SCC7 cells39. ■ Increased proliferation and migration of IL-1β–treated DOK and TW2.6 cells201. |
| Pancreatic Cancer | ■ Reduced pancreatic neoplasia and improved survival of Aim2-deficient KCPink1−/− and KCPark2−/− mice51. ■ Delayed malignant progression and extended survival in Nlrp3−/− KC mice48. ■ Reduced PDA tumor growth in the pancreata of Nlrp3−/−, Asc−/− and Casp1−/− mice48. ■ Reduced Panc02 tumor growth in chimeric WT mice adoptively transferred with Casp1−/− BMCs199. |
N/A |
| Hematopoietic neoplasms | ■ Delayed multiple myeloma progression and prolonged survival in Nlrp1−/− and Il18−/− mice challenged with myeloma cell lines52. | ■ Enhanced proliferation of IL-18–treated Pfeiffer cells38. |
| Malignant Mesothelioma | ■ Delayed onset and reduced tumor incidence in Asc−/− mice202. | N/A |
Abbreviations: AOM, azoxymethane; BMCs, bone marrow cells; BMSCs, bone marrow stem cells; DEN, N,N-diethylnitrosamine; DMBA, dimethylbenz[a]anthracene; DSS, dextran sodium sulfate; HCC, hepatocellular carcinoma; KC, Pdx1creKrasG12D/+; LLC, Lewis lung carcinoma; MCA, methylcholanthrene; N/A, information not available;
NSCLC, non–small cell lung cancer; PDA, pancreatic ductal adenocarcinoma; pDCs, plasmacytoid dendritic cells; SCID, severe combined immunodeficiency; TPA, 12-O-tetradecanoylphorbol-13-acetate; 4-NQO; 4-nitroquinoline 1-oxide; 5-FU, 5-Fluorouracil.
Cell lines: A375, B16F10, HMB2, VUP, SK23, MJM, WM115, 1205Lu, Hs294T: melanoma; RM-1, PC3-ML, DU145: prostate cancer; E0771, Py8119, PyT8, MDA-MB-231, MDA-MB-435, MDA-MB-453, 4T1, BT474, MCF-7: breast cancer; PC, A549, H1703, H1975: lung cancer; T241: fibrosarcoma; BGC-823, AGS, MKN1: gastric cancer; CT26, MC38, HCT116, HPCC, HT29, Caco-2, HCA7, SW620: colon cancer; Hepa1–6: liver cancer; 9L, C6, SR-B10, GL-261, U87, T98G, U251: glioma; UT-SCC7, WSU-HN6, CAL27, DOK, TW2.6: squamous cell carcinoma; Panc02: Pancreatic cancer