Background
Immunotherapy plays an important role in cancer treatment, but the efficacy of immunotherapy is not ideal in most breast cancers. Thus, finding new treatment strategies is urgently needed. We previously identified a palmitoyltransferase Zinc Finger DHHC-Type Containing 1 (ZDHHC1) as a novel tumour suppressor, which was first discovered to positively regulate the innate immune response. However, its role in breast cancer immunity is still unknown.
Methods
The project aims to utilize Mass Cytometry and other methods to explore how ZDHHC1 regulates autophagy and affects tumour immunity in breast cancer.
Results
Online single-cell RNA sequencing analysis showed that in the immunotherapy-sensitive breast cancer mice model, Zdhhc1 significantly reduced in malignant cells after immunotherapy. Further studies showed that overexpression of ZDHHC1 led to the formation of autophagosomes. ZDHHC1 also downregulated SIRT2 in the cytoplasm, and upregulated acetylated FOXO1. Inhibiting palmitoyltransferase activity restored the inhibition of p62, and SIRT2 was predicted to have the palmitoylation site. Thus, ZDHHC1 may palmitoylate SIRT2 in the cytoplasm, reducing the interaction with FOXO1, and increasing the acetylation of FOXO1, thereby promoting autophagy.
Conclusions
The ZDHHC1-mediated autophagy may influence the tumour immune microenvironment, thereby increasing the sensitivity of breast cancer immunotherapy. The study will reveal the new mechanism of tumour immunity in breast cancer, and provide new ideas and theoretical basis for the transformation of breast cancer immunotherapy strategies.