P02.07 Innate immunity atlas of hepatocellular carcinoma unravels the differentiation hierarchy of myeloid NK cells and MDSCs

Abstract

immunohistochemistry. Paraffin sections were stained with hematoxylin and eosin (H&E) or Ki67 according to standard methods. For immunohistochemistry, cryosections were stained overnight at 4°C with fluorescent antibodies. Results H&E images confirmed that transgenic Apc 1322T mice lacking IL-25 had smaller tumours and showed less dysplasia than Apc 1322T mice with normal IL-25 expression. Ki67 staining showed that tumours express higher Ki67 levels than adjacent normal intestinal tissue. The tumour-associated tertiary lymphoid structures (TATLS) of Apc 1322T mice lacking IL-25 appeared larger, indicating a more robust anti-tumour immune response.Likewise, Apc 1322T mice lacking ILC2s had smaller, less dysplastic tumours. TATLS in these mice were bigger than mice with ILC2s but smaller than Apc 1322T mice lacking IL-25, indicating that IL-25 may act via additional protumourigenic cell types.Immunohistochemistry confirmed the presence of ILC2s, as well as MDSCs the tumours of Apc 1322T mice, suggesting that these cells create an immunosuppressive niche. Conclusions This pilot study confirms that genetic ablation of either IL-25 or ILC2s promotes anti-tumour immune reactions and decreases tumour size, correlating with reduced intestinal tumour proliferative capacity and dysplasia. Mice lacking IL-25 or ILC2s had larger TATLS, which are known to be associated with improved prognosis in patients. This study, along with previous data, highlights the potential therapeutic benefit of targeting the IL-25-ILC2 axis for colorectal cancer. Further studies are required to bring this from bench to bedside.