Abstract 79P
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.
Editorial acknowledgement
Clinical trial identification
Legal entity responsible for the study
Xiaohe Zhou, Xuru Wang, Fengjiao Zhu.
Funding
The National Natural Science Foundation, China.
Disclosure
The author has declared no conflicts of interest.
Resources from the same session
62P - Role of IL6 (C-174G) polymorphism in the development of cervical intraepithelial neoplasia
Presenter: Tatyana Abakumova
Session: Cocktail & Poster Display session
Resources:
Abstract
63P - The impact of disruption of melatonin secretion on the structural-functional changes of the microbiome and the role of the melatonin-microbiome axis in the initiation of carcinogenesis
Presenter: Alexandre Tavartkiladze
Session: Cocktail & Poster Display session
Resources:
Abstract
64P - Acidosis induces ferroptosis of breast cancer via ZFAND5/SLC3A2 axis with the synergistic effect of metformin and facilitates M1 macrophage polarization
Presenter: Hanchu Xiong
Session: Cocktail & Poster Display session
Resources:
Abstract
65P - Transmembrane distribution of phosphatidylethanolamine in plasma membrane of ovarian cancer cells under conditions mimicking tumor microenvironment
Presenter: Darya Savenkova
Session: Cocktail & Poster Display session
Resources:
Abstract
66P - Metabolic regulation of GMP- and MDP-derived macrophages in glioblastoma
Presenter: Liam Wilson
Session: Cocktail & Poster Display session
Resources:
Abstract
67P - Inflammation status and sarcopenia synergistically impact outcomes in cancer patients (pt) treated with ImmunOtherapy (IO) within the framework of a Molecular Pre-screening program (MP) and a spEcial Medication (ME) program
Presenter: Lucia Notario Rincon
Session: Cocktail & Poster Display session
Resources:
Abstract
68P - The role of systemic reprogramming of GMPs in improving outcomes in glioblastoma
Presenter: Aline Atallah
Session: Cocktail & Poster Display session
Resources:
Abstract
69P - Integrated OMIC analysis reveals arginine and proline metabolism plays critical role in hypoxia-induced oral squamous cell carcinoma
Presenter: Avinash Singh
Session: Cocktail & Poster Display session
Resources:
Abstract
70P - Individualising methotrexate dose based on MTHFR gene polymorphisms in acute lymphoblastic leukemia
Presenter: Meher Konatam
Session: Cocktail & Poster Display session
Resources:
Abstract
71P - Single nucleotide polymorphisms in the folate metabolic pathway genes and global DNA methylation in ovarian cancer
Presenter: Sandro Surmava
Session: Cocktail & Poster Display session
Resources:
Abstract