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Liver cancer is the third leading cause of cancer-related deaths worldwide, and hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver
Because the HCC tumor microenvironment (TME) is highly complex, with multiple cellular components that make up various functional units and cell neighborhoods (CN), traditional immunohistochemistry or immunofluorescence methods are difficult to meet the needs of multi-parameter detection.
Recently, a research team led by Professor Liang Tingbo and Researcher Sheng Jianpeng from Zhejiang University has made breakthroughs in the field of HCC immunotherapy
This study used IMC to quantify the expression and location information of 36 markers in FFPE slice samples from 134 HCC patients and 7 healthy donors, and obtained 562 high-dimensional tumor pathological images with subcellular spatial resolution
Fig1.
How to parse the image information and establish a connection with clinical data has become the key to the next step of research
Organizational topology analysis of HCC microenvironment
For tissue topology analysis, the researchers first use CellProfiler software to segment each cell in the tissue image to obtain marker expression data at the single-cell level
Fig 2.
Specific distribution of immune cells and stromal cells among the three main types of HCC
Analyzing multiple regions in each liver cancer patient sample, three main types of TME (Type I-III) were found in HCC, with different matrix and immune cell distribution patterns, which correspond to the dedifferentiation of hepatocytes Different stages
Fig 3.
Single cell analysis of the differential distribution of cells in different TMEs
The author further studied the relationship between the dedifferentiation process and the changes in the tumor microenvironment, using tSNE to analyze at the single-cell level, and adding meta-cluster (1-22) annotations to the tSNE diagram (Fig 4A)
Fig 4.
Correlation between cell neighborhood in liver cancer microenvironment and patient survival
The city in which we live is composed of different communities (such as industry, housing, or agriculture).
Fig 5.
Depletion of Kupffer cells enhances tumor response to PD-1 therapy
Next, the author constructed a mouse model and used IMC and other technologies to prove that the depletion of Kupffer cells in the liver greatly enhances the T cell response, reduces the growth of liver tumors and the tumor is sensitive to anti-PD-1 treatment
.
It highlights the potential of Kupffer cells to specifically target rather than block bone marrow cells as a new type of immunotherapy for HCC treatment
.
This study successfully used Fluidig m's tissue imaging mass spectrometry flow cytometry system to conduct in-depth topological analysis of the hepatocellular carcinoma tumor immune microenvironment
.
Unlike traditional immunohistochemistry or immunofluorescence, IMC uses metal elements as antibody labels and uses a mass spectrometry system for signal detection
.
In principle, it avoids the influence of fluorescence cross-color, tissue background and other factors on the results.
It can detect dozens of proteins in one scan.
It has become an effective tool for tumor microenvironment topology analysis and is ideal for studying healthy tissues or pathological tissues.
Means
.
references:
1 Sheng, JP, Zhang, JL, Wang L.
et al.
"Topological analysis of hepatocellular carcinoma tumour microenvironment based on imaging mass cytometry reveals cellular neighbourhood regulated reversely by macrophages with different ontogeny.
" Gut.
12 July 2021, doi: 10.
1136/ gutjnl-2021-324339.