mass-cytometry-analysis-systemic-local-immune-responses

Mass Cytometry Analysis of Systemic and Local Immune Responses in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is one of the most common and deadliest forms of liver cancer worldwide. Despite advances in treatment, the prognosis for ...

Zhejiang University School of Medicine

The  genus is widely used as a traditional Chinese medicine and functional food. Many of the chemical constituents of the genus  were reported previously. In this review, in addition to the polysaccharides, we have enumerated 355 chemical constituents and nutrients, including 22 glycerogalactolipids, 29 phenylpropanoids, 10 coumarins, 13 lignans, 32 flavonoids, 37 amides, 72 alkaloids, four anthraquinones, 32 organic acids, 39 terpenoids, 57 sterols, steroids, and their derivatives, five peptides and three other constituents. This comprehensive study could lay the foundation for further research on the  genus.

Systematic Review of Chemical Constituents in the Genus Lycium (Solanaceae).

Hepatocellular carcinoma (HCC) tumour microenvironment (TME) is highly complex with diverse cellular components organising into various functional units, cellular neighbourhoods (CNs). And we wanted to define CN of HCC while preserving the TME architecture, based on which, potential targets for novel immunotherapy could be identified.

Topological analysis of hepatocellular carcinoma tumour microenvironment based on imaging mass cytometry reveals cellular neighbourhood regulated reversely by macrophages with different ontogeny.

Hypoxia is a typical characteristic of most solid malignancies, which has multiple effects on malignant phenotypes and biological behaviors of tumors including epithelial-mesenchymal-transition (EMT), invasion, migration, metastasis, autophagy, stem cell maintenance, pathological angiogenesis, drug resistance, and immunosuppression. Rcentlyumoand reversing the tumor hypoxic environment via nanotechnology has emerged as a novel therapeutic approach for the treatment of malignancies. The main strategies related to nanotechnology to alleviate or ameliorate hypoxic environment are as follows: (1) Bringing external oxygen to tumor hypoxic microenvironment; (2) Generating oxygen based on nanotechnology ; (3) Regulating the structure of the tumor microenvironment; (4) Decreasing oxygen consumption in the tumor microenvironment. In this review, we will discuss these nanotechnologies in detail.

Recent Advancements of Nanotechnology-Based Strategies for Overcoming Tumor Microenvironment Hypoxia.

Hypoxia in tumor microenvironment (TME) represents an obstacle to the efficacy of immunotherapy for pancreatic ductal adenocarcinoma (PDAC) through several aspects such as increasing the expression of immune checkpoints or promoting fibrosis. Reversing hypoxic TME is a potential strategy to improve the validity of immune checkpoint blockade (ICB).

Oxygen microcapsules improve immune checkpoint blockade by ameliorating hypoxia condition in pancreatic ductal adenocarcinoma.

Both colorectal and gastric cancer are lethal solid-tumor malignancies, leading to the majority of cancer-associated deaths worldwide. Although colorectal cancer (CRC) and gastric cancer (GC) share many similarities, the prognosis and drug response of CRC and GC are different. However, determinants for such differences have not been elucidated. To avoid genetic background variance, we performed multi-omics analysis, including single-cell RNA sequencing, whole-exome sequencing, and microbiome sequencing, to dissect the tumor immune signature of synchronous primary tumors of GC and CRC. We found that cellular components of juxta-tumoral sites were quite similar, while tumoral cellular components were specific to the tumoral sites. In addition, the mutational landscape and microbiome contributed to the distinct TME cellular components. Overall, we found that different prognoses and drug responses of GC and CRC were mainly due to the distinct TME determined by mutational landscape and microbiome components.

Genetic mutation and tumor microbiota determine heterogenicity of tumor immune signature: Evidence from gastric and colorectal synchronous cancers.

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer that typically demonstrates resistance to chemotherapy. Tumor-associated macrophages (TAMs) are essential in tumor microenvironment (TME) regulation, including promoting chemoresistance. However, the specific TAM subset and mechanisms behind this promotion remain unclear. We employ multi-omics strategies, including single-cell RNA sequencing (scRNA-seq), transcriptomics, multicolor immunohistochemistry (mIHC), flow cytometry, and metabolomics, to analyze chemotherapy-treated samples from both humans and mice. We identify four major TAM subsets within PDAC, among which proliferating resident macrophages (proliferating rMφs) are strongly associated with poor clinical outcomes. These macrophages are able to survive chemotherapy by producing more deoxycytidine (dC) and fewer dC kinases (dCKs) to decrease the absorption of gemcitabine. Moreover, proliferating rMφs promote fibrosis and immunosuppression in PDAC. Eliminating them in the transgenic mouse model alleviates fibrosis and immunosuppression, thereby re-sensitizing PDAC to chemotherapy. Consequently, targeting proliferating rMφs may become a potential treatment strategy for PDAC to enhance chemotherapy.

Multi-omics analysis reveals the chemoresistance mechanism of proliferating tissue-resident macrophages in PDAC via metabolic adaptation.

Ulcerative colitis is a chronic inflammatory bowel disorder with cellular heterogeneity. To understand the composition and spatial changes of the ulcerative colitis ecosystem, here we use imaging mass cytometry and single-cell RNA sequencing to depict the single-cell landscape of the human colon ecosystem. We find tissue topological changes featured with macrophage disappearance reaction in the ulcerative colitis region, occurring only for tissue-resident macrophages. Reactive oxygen species levels are higher in the ulcerative colitis region, but reactive oxygen species scavenging enzyme SOD2 is barely detected in resident macrophages, resulting in distinct reactive oxygen species vulnerability for inflammatory macrophages and resident macrophages. Inflammatory macrophages replace resident macrophages and cause a spatial shift of TNF production during ulcerative colitis via a cytokine production network formed with T and B cells. Our study suggests components of a mechanism for the observed macrophage disappearance reaction of resident macrophages, providing mechanistic hints for macrophage disappearance reaction in other inflammation or infection situations.

Selective oxidative protection leads to tissue topological changes orchestrated by macrophage during ulcerative colitis.

Eyelid tumors pose diagnostic challenges due to their diverse pathological types and limited biopsy materials. This study aimed to develop an artificial intelligence (AI) diagnostic system for accurate classification of eyelid tumors. Utilizing mass spectrometry-based proteomics, we analyzed proteomic data from eight tissue types and identified eighteen novel biomarkers based on 233 formalin-fixed, paraffin-embedded (FFPE) samples from 150 patients. The 18-protein model, validated by an independent cohort (99 samples from 60 patients), exhibited high accuracy (84.8%), precision (86.2%), and recall (84.8%) in multi-class classification. The model demonstrated distinct clustering of different lesion types, as visualized through UMAP plots. Receiver operator characteristic (ROC) curve analysis revealed strong predictive ability with area under the curve (AUC) values ranging from 0.80 to 1.00. This AI-based diagnostic system holds promise for improving the efficiency and precision of eyelid tumor diagnosis, addressing the limitations of traditional pathological methods.

Article	Year
Systematic Review of Chemical Constituents in the Genus Lycium (Solanaceae). Molecules (Basel, Switzerland)\| PubMed ID: 28629116	2017
Topological analysis of hepatocellular carcinoma tumour microenvironment based on imaging mass cytometry reveals cellular neighbourhood regulated reversely by macrophages with different onto... Gut\| PubMed ID: 34253573	2022
Recent Advancements of Nanotechnology-Based Strategies for Overcoming Tumor Microenvironment Hypoxia. Frontiers in bioscience (Landmark edition)\| PubMed ID: 35638412	2022
Oxygen microcapsules improve immune checkpoint blockade by ameliorating hypoxia condition in pancreatic ductal adenocarcinoma. Bioactive materials\| PubMed ID: 35702611	2023
Genetic mutation and tumor microbiota determine heterogenicity of tumor immune signature: Evidence from gastric and colorectal synchronous cancers. Frontiers in immunology\| PubMed ID: 36420271	2022
Multi-omics analysis reveals the chemoresistance mechanism of proliferating tissue-resident macrophages in PDAC via metabolic adaptation. Cell reports\| PubMed ID: 37285267	2023
Selective oxidative protection leads to tissue topological changes orchestrated by macrophage during ulcerative colitis. Nature communications\| PubMed ID: 37344477	2023
AI-driven eyelid tumor classification in ocular oncology using proteomic data. NPJ precision oncology\| PubMed ID: 39715816	2024

Yaxing Zhao

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