Cell discovers the "hub" of immune cells hidden in tumors

Tumors in the human body are like a city in war, with cancer cells, immune cells, blood vessels, signal molecules and surrounding tissues bustling with hustle and bustle

Now a group of researchers has a new understanding of this organizational structure

The results of this research are published in Cell magazine

Research results point out that in certain types of colorectal cancer, the interaction network of immune cells is more likely to be "discovered" by the immune system

"By analyzing the activity of each cell in the tumor, we can monitor the conversation between the cells and distinguish the tissues that we couldn't see before," the co-director of the Broad Institute's Cell Circuits Program (cell Circuits Program) and senior researcher.

Tumors with different immune responses

At the genetic and molecular level, colorectal cancer can be divided into two types

Postdoctoral researchers Karin Pelka, Matan Hofree and Jonathan Chen are the first authors of this new study and are also members of the Regev and Hacohen laboratories.

"Complex systems like tumors require a team of researchers with different expertise to accept the research challenge

Previously, researchers used this data to cluster cells into discrete categories and then describe the gene expression patterns of each cell type

Using these new analytical tools, the research team found that specific genetic programs and cell types are only present in MMRd tumors, which are more sensitive to immunotherapy

Immune activity center

Scientists then looked for genetic programs that coordinate with each other in different cell types—when the expression of one genetic program increases or decreases, the other program also changes

"We realized that understanding the individual parts and cell types of tumors does not tell us the whole story," Pelka said.

The analysis revealed that malignant tumor cells and two types of immune cells—T cells and bone marrow cells—may interact and initiate specific genetic programs

Regev said: "Observing the co-mutation process in different cell types provides a new perspective for this complex tumor ecosystem

The scientists also noticed that compared with MMRp tumors, MMRd tumors (which respond better to immunotherapy) have a higher incidence of central cells

Hofree said: "It is shocking that some of the strongest interaction signals we predicted in our computational analysis are actually the observable centers of cell space organization

"It turns out that the immunity of these tumors is quite organized, not scattered," Chen said.
"Especially when we look at MMRd tumors, these clear structures contain active immune cells
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The research team is currently planning to conduct research to use the same method to track how immune cells in colorectal cancer change their gene expression patterns and communication with each other during immunotherapy
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Rozenblatt-Rosen said: "We hope that this research will provide a framework for future research on cancer cell tissues
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(Biocom)

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Spatially organized multicellular immune hubs in human colorectal cancer

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