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1. Introduction
2. Interest in Hepatocellular Carcinoma (HCC)
3. HCC and biliary tumors in the US
4. 10-year mortality trend
5. Estimated age-standardized mortality rates in 2020
6. Risk factors
7. NAFLD causes selective CD4+ T cell loss and promotes hepatocarcinogenesis
8. NASH promotes hepatocarcinogenesis
9. Selective CD4+ T cell loss in mice with NASH
10. Hepatocytes from mice with NASH cause selective CD4+ T cell death
11. Linoleic acid causes selective CD4+ T cell loss
12. NAC treatment prevents CD4+ T cell loss
13. Non-Alcoholic Fatty Liver Disease (NAFLD)
14. Steatohepatitis impairs T cell-directed immunotherapies against liver tumors in mice
15. NAFLD impairs the efficacy of M30
16. N-acetyl cysteine restores M30 effect in NAFLD
17. Anti-PD1 treatment efficacy is CD8 T cell dependent
18. Metformin treatment in mice with NAFLD
19. Experimental set-up
20. Anti-PD1 treatment in hepatic tumors in NASH
21. NASH activates CD8+ T cells
22. Effect of anti-PD1 on T cells in NASH
23. PD-1 inhibition for HCC in the context of NASH
24. CXCR6+ CD8+ T cells in mice with NAFLD
25. Anti-PD1 treatment in murine NAFLD models
26. In vivo CD8+ T cell imaging studies (1)
27. In vivo CD8+ T cell imaging studies (2)
28. In vivo CD8+ T cell imaging studies (3)
29. CD8+ TILs mobility is impaired in NAFLD
30. In vivo analysis of CD8+ T cell subsets
31. In vitro CD8+ T cell imaging studies
32. Metformin and CD8+ T cell response to anti-PD1 (1)
33. Metformin and CD8+ T cell response to anti-PD1 (2)
34. Metformin restores efficacy of anti-PD-1 therapy in NASH-HCC
35. Metformin and VEGF pathway targeting antibody
36. Metformin treatment summary
37. CXCR2 inhibition and NASH-HCC
38. Aspirin and HCC and liver-related mortality
39. Mouse tumor monitoring using micro-CT
40. Platelet depletion promotes HCC growth in NAFLD
41. P2Y12 inhibition promotes HCC in NAFLD (1)
42. P2Y12 inhibition promotes HCC in NAFLD (2)
43. P2Y12 inhibition and liver metastasis in NAFLD
44. Unexpected results
45. Expression of CD40L on activated platelets
46. Platelets release more CD40L in NAFLD
47. Circulating levels of CD40L in patients with NAFLD
48. CD40L neutralization and tumor growth in NAFLD
49. Platelet-derived CD40L controls HCC growth in mice with NAFLD
50. Platelets activate hepatic T cells in NAFLD
51. NAFLD-liver tissue supernatant induces CD40L in megakaryocytes
52. Liver macrophage produce IL-12
53. Platelets impair HCC growth in NAFLD via CD40L
54. NAFLD patients are more likely to use clopidogrel
55. NASH impacts adaptive immune response and anti-PD1 therapy for HCC
56. HCC: from the perspective of an immunologist (1)
57. HCC: from the perspective of an immunologist (2)
58. Cell composition of healthy adult liver
59. Innate lymphoid cells (ILCs)
60. Innate lymphoid cells (characteristics)
61. Cancer immunosurveillance
62. Immune environment (1)
63. Immune cell composition by region in HCC
64. Cytokine gradients in the HCC environment
65. IL33 expression correlates with survival
66. Immune environment (2)
67. ILC FACS analysis
68. Distribution of ILCs in HCC
69. Immune environment (3)
70. ILC2 plasticity and tSNE analysis of liver lin- cells
71. 11-gene signature of mature c-Kitneg ILC2s
72. ILCs: Summary (1)
73. ILCs: Summary (2)
74. Mucosal-Associated Invariant T cells (MAITs) -
75. MAITs - overview
76. MAITs in human and mice
77. 5-OP-RU + CpG treatment activates MAIT cells in vivo
78. MAIT cells inhibit tumor growth upon 5-OP-RU + CpG treatment
79. MAITs Summary
80. Talk summary

Topics Covered

• Immunotherapy of hepatocellular carcinoma (HCC)
• Liver metastasis
• Risk factors for HCC
• Fatty liver disease
• Non-alcoholic fatty liver disease (NAFLD)
• Non-alcoholic Steatohepatitis (NASH)
• The role of immune cells in HCC
• Metformin treatment
• P2Y12 inhibition and HCC
• NAFLD and CD40L accumulation in platelets
• Innate lymphoid cells (ILCs)
• Immune cell composition in HCC
• Mucosal-associated invariant T cells (MAITs)
• CD4 and CD8 T cells

Links

Series:

• Immunotherapy of Cancer

Categories:

• Cancer
• Immunology

Therapeutic Areas:

• Immunology & Inflammation
• Oncology

Talk Citation

Publication History

• Published on June 29, 2023

Financial Disclosures

• Prof. Tim Greten has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.