Abstract 61P
Background
Cancer-associated fibroblasts (CAFs) are the most prominent stromal cells in the tumor microenvironment, playing a significant role in tumor progress. However, the specific mechanisms underlying CAF formation and their role in remodeling the tumor microenvironment remain unclear. Previous studies have demonstrated that tumor cell-released autophagosomes (TRAPs) can arrival to lung tissue and regulate the function of lung fibroblasts to form premetastatic niche.
Methods
Primary breast adipose fibroblasts (NFs) were obtained from fourth mammary fat pads of mice, and co-cultured with TRAPs for 48 hours. The chemokines in collected supernatant were measured by ELISA. The expression of PD-L1 on the surface of fibroblasts and the ability to inhibit T cells were measured by flow cytometry (FCM). DAMPs on the TRAP surface blocked by antibodies, and fibroblasts pretreated with inhibitors were used to detect the ligand receptors between TRAP and NFs. Mouse experiments were performed as follows: 1)Tumor-bearing mice were constructed using TRAP low-expression cell lines (Beclin1KD/Raba8a KD); 2) NFs and 4T1 cells, with or without TRAP stimulation, were mixed and implanted in mice to detect the proportion and function of various cells in the tumor microenvironment by FCM.
Results
In vitro experiments revealed that the proteins (HSP27/70) on the surface of TRAP bind to TLR4 on NFs, exerting their functions via the HSP27/70-TLR4-MyD88- NF-κB signal cascade, ultimately expressing higher levels of PD-L1. Compared to the normal control (NC) group, the proportion of neutrophils and monocytes in the tumor microenvironment decreased, opposite T cells increased. Furthermore, the ability of T cells to secrete IFN-γ partially recovered. The level of PD-L1 on the surface of fibroblasts decreased, and their ability to inhibit T cells weakened.
Conclusions
TRAPs induce the formation of inflammatory and immune-suppressive fibroblasts by secreting CXCL1/2 and CCL5 to attract neutrophils and monocytes to the tumor microenvironment. Additionally, TRAPs directly inhibit T cells, ultimately contributing to the formation of the tumor microenvironment.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
X. Zhou, X. Wang, F. Zhu.
Funding
National Natural Science Foundation, China.
Disclosure
The author has declared no conflicts of interest.
Resources from the same session
415P - Initial experience in a real-world Asian cohort with a circulating tumor DNA (ctDNA) mutation-based multi-cancer early detection (MCED) assay
Presenter: Steven Tucker
Session: Poster Display
Resources:
Abstract
416P - Three-dimensional bioprinting model of ovarian cancer for identification of patient-specific therapy response
Presenter: Jiangang Zhang
Session: Poster Display
Resources:
Abstract
417P - Early experience in using plasma-only multi-omic minimal residual disease testing in early-stage colorectal cancer patients from Asia and the Middle East
Presenter: Shaheenah Dawood
Session: Poster Display
Resources:
Abstract
418P - Decoding the intricate cellular makeup of immune-related adverse events using single-cell and spatial analysis
Presenter: Dmitrii Shek
Session: Poster Display
Resources:
Abstract
420P - Combinatory genomic and transcriptomic sequencing of Chinese KRAS mutant non-small cell lung cancer revealed molecular and inflammatory heterogeneity in tumor microenvironment
Presenter: Xuchao Zhang
Session: Poster Display
Resources:
Abstract
421P - Comprehensive genomic profiling (CGP) unravels somatic BRCA (sBRCA) and homologous recombinant repair (HRR) gene alterations across multi-cancer spectrum
Presenter: Ramya Kodandapani
Session: Poster Display
Resources:
Abstract
422P - CD8Teff distinguished tumor immunotyping heterogeneity and enables precision immunotherapy
Presenter: luhui Mao
Session: Poster Display
Resources:
Abstract
423P - Insights into clinically actionable biomarkers in an Indian cancer cohort of 1000 patients using comprehensive genomic profiling (CGP)
Presenter: Mithua Ghosh
Session: Poster Display
Resources:
Abstract
424P - MD Anderson Cancer Center global precision oncology decision support (Glo-PODS) clinical trial genomic support: Pilot program at the Prince of Wales Hospital (Chinese University of Hong Kong - CUHK)
Presenter: Brigette Ma
Session: Poster Display
Resources:
Abstract
425P - Engineered <italic>Lactococcus lactis</italic> as a personalized cancer vaccine platform induces antitumour immunity via membrane-inserted peptide for neoantigens
Presenter: Meng Zhu
Session: Poster Display
Resources:
Abstract