Monday, April 19, 2021

Internal Differences: A New Method for Seeing into Cells

Recommendable! "Why does the immune system fail to recognize and kill cancer cells?"

"... [researchers] had previously made significant inroads into seeing into cells when they developed single cell RNA-sequencing – a means of sequencing all of the RNA in thousands of individual cells at once. The new technique, called INs-seq (intracellular staining and sequencing) ... enables scientists to measure, in addition to the RNA, numerous proteins, processes and biochemical pathways occurring inside each of the cells. ... help them draw much finer distinctions between different cell subtypes and activities than is possible with existing methods, most of which are able to measure surface proteins only. ...
Distinguishing between subtypes of cells that seem identical from the outside, such as inhibitory- versus effector-immune cells, may be crucial to when it comes to fighting off cancer.

Although the principal groups of immune cells had been identified many decades ago, there are hundreds of subtypes with many different functions, which haven’t been classified. “Specific immune subtypes, for example, may play a role in promoting cancer or enabling it to evade the immune system, provoke tissue destruction by overreacting to a virus or act mistakenly in autoimmune syndromes, attacking our own body. Until now, there was no sufficiently sensitive means of telling these apart from other subtypes that appear identical from the outside,” ..."

"... Here, we introduce INs-seq, an integrated technology for massively parallel recording of single-cell RNA sequencing (scRNA-seq) and intracellular protein activity. We demonstrate the broad utility of INs-seq for discovering new immune subsets by profiling different intracellular signatures of immune signaling, transcription factor combinations, and metabolic activity. ...
Why does the immune system fail to recognize and kill cancer cells, and why does immunotherapy for most tumor types often fail? In searching for an answer, they asked whether cancers might hijack and manipulate particular immune cells to “defend” the cancer cells from the rest of the immune system. ...
Indeed, the team succeeded in identifying T-cell-blocking immune cells, which belonged to a general group known as myeloid cells ... Although this particular subset of suppressive myeloid cells was new, it was distinguished by a prominent signaling receptor that ... had seen before, called TREM2. This receptor is critical for the activity of the cells that block the actions of tumor-killing T cells; and normally cells bearing this receptor are crucial for preventing excess tissue damage after injury or calming an inflammatory immune response. ... had also come across a version of this receptor in other immune cells involved in Alzheimer’s disease, metabolic syndrome and other immune-related pathologies. ..."

Internal Differences: A New Method for Seeing into Cells The new technology may help answer outstanding questions about the immune system, cancer, Alzheimer’s, and more

Here is the underlying research article:

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