Abstract A047: Activation of conventional type 2 dendritic cells (cDC2) by anti-CD47 may enhance antitumor T cell function in mouse liver cancer models
Journal
Cancer Immunology Research
Journal Volume
12
Journal Issue
10_Supplement
Start Page
A047-A047
ISSN
2326-6074
Date Issued
2024-10-18
Author(s)
Abstract
Anti-CD47 has been extensively studied for its effects on activating phagocytosis by blocking the ‘don’t eat me’ signal presented by CD47 expressed on cancer cells. This study explored the effects of anti-CD47 on enhancing antigen presentation by dendritic cells and improving antigen-specific antitumor immunity. Mouse Hepa1-6 liver cancer cells with or without over-expression of LCMV-GP protein and splenocytes from P14 transgenic mice were used to test antigen-specific antitumor immunity. Bone marrow-derived conventional type 1 and type 2 dendritic cells (cDC1 and cDC2) or MutuDC1/ DC2 cell lines were co-cultured with CD8 T cells with or without exhaustion. Effects of anti-CD47 on the cross-priming ability of DC were analyzed by T cell proliferation (CSFE labeling), activation (expression of IFNγ, granzyme B, TNFa, and IL-2), cell killing (in vitro cytotoxicity assay) and T cell exhaustion (LAG3, TOX, PD1 expression). In vivo studies indicated that anti-CD47 treatment may suppress tumor growth, activate intra-tumoral cDC2 but not type 1 dendritic cells (cDC1), and delay CD8 T cells from entering terminal exhaustion in the tumor microenvironments. In vitro studies indicated that anti-CD47 may enhance the priming ability of cDC2, but not cDC1, and increase ISG15 expression in cDC2. When co-cultured with exhausted T cells, anti-CD47-treated cDC2 may delay the exhaustion process and restore antigen-specific effector function and cytotoxic capacity. Conclusion: Anti-CD47 may enhance antitumor T cell function in mouse liver cancer models by activation of cDC2, which may serve as a new strategy of developing immunotherapeutic agents for liver cancer (supported by grants NSTC 111- 2314-B-002-039 and 113-2314-B-002-113-MY3).
Publisher
American Association for Cancer Research (AACR)
Type
journal article