2024 Asia Conference on Lung Cancer (ACLC) - Poster & ePosters-PP01.36

PP01.36 - Xiru Quan

Pdf Summary

The study examines the role of Alpha-Kinase 1 (ALPK1), a pattern recognition receptor, in cancer immunotherapy, focusing on its impact when combined with anti-PD1 treatment. ALPK1 is activated by bacterial ADP-Heptose, a metabolite found in many Gram-negative and some Gram-positive bacteria. This activation results in the phosphorylation of TIFA, enabling the oligomerization of TIFA and TRAF6, thereby activating the NF-κB pathway and inducing innate immune responses that produce proinflammatory chemokines and cytokines.<br /><br />The research, conducted at Shanghai Chest Hospital, explores how ALPK1 activation affects the efficacy of anti-PD1 therapy in mouse tumor models. Female C57BL/6 mice were injected with SJT-1601 or MC38 tumor cells and randomly divided into four groups: a control group, a PD-1 monotherapy group, an ADP-Heptose monotherapy group, and a combination treatment group. Treatments were administered intraperitoneally with either 200 μg of anti-PD1 monoclonal antibody, 40 μg of ADP-Heptose, or both, on days 7, 10, 13, and 16 post-tumor implantation.<br /><br />Results showed that while PD-1 alone had a significant anti-tumor effect reducing tumor size and growth compared to the control, the combination of ADP-Heptose with PD-1 diminished this efficacy. Flow cytometry analysis revealed increased neutrophil infiltration in the tumor microenvironment (TME) in the combination group compared to the PD-1 group alone. This suggests that ALPK1 activation by ADP-Heptose recruits neutrophils, contributing to an immunosuppressive TME, which in turn impairs the effectiveness of PD-1 therapy. The findings highlight the need to consider the potential for innate immune receptor activation to inadvertently undermine immunotherapy outcomes.

Keywords

ALPK1

cancer immunotherapy

anti-PD1 treatment

ADP-Heptose

NF-κB pathway

innate immune responses

neutrophil infiltration

tumor microenvironment

Shanghai Chest Hospital

immunosuppressive TME