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🏥 | It turns out that cancer cells "suck out" the mitochondria of immune cells and grow.


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It turns out that cancer cells "suck out" the mitochondria of immune cells and grow.

 
If you write the contents roughly
According to the research group, "combining immune checkpoint inhibitors and substances that inhibit nanotube formation like this may lead to the development of new therapeutic agents."
 

A research group at a well-known American engineering university and hospital has announced that cancer cells will attack immune cells at the nano-level. → Continue reading

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Immune checkpoint inhibitor

Immune checkpoint inhibitor(Immune checkpoint blockade / immune checkpoint inhibitor: ICI)T cellsIt is an inhibitor of the system that suppresses the activity of (the "immune checkpoint system" described later).[1]..New generationcancerWith treatmentJapaneseDeveloped by[1][2]..Responsible for checkpoints (check mechanism) to suppress immunity分子It is so called because it targets.For the first timeClinicalThe name of the drug used forIpilimumab(The product name in Europe and the United States is "Yervoy")[3].

the term

As a term, "immune checkpoint molecule" or "immune checkpoint" is a molecule that T cells and cells that bind to T cells have on the membrane surface, etc. in the current 2010s, and further have an immunosuppressive function ( A molecule (receptor-like)[4].

If you want to specify the T cell immunosuppressive system, you may specify it as "immune checkpoint system".[5].

By stimulating the receptor, such as the receptors PD-1 and CTLA-4 described below,ImmunologyA type of receptor whose function is suppressed is called an inhibitory receptor.[6].

Overview

T cells have a mechanism on the surface of T cells called "immune checkpoints" that suppresses immunity when expressed so as not to attack the cells of the individual organism itself (the mechanism of immune checkpoints will be described later). ) However, this mechanism cannot distinguish cancer cells and misidentifies them as companions.As of 2018, molecules that are generally regarded as "immune checkpoints" of immune checkpoint inhibitors (temporarily PD-L1 / PD-1 and CD80 / CTLA-4 as general cell / T cell formats) areMHCIs a different molecule. MHC is also on the cell surface, but PD-L1 / PD-1 and CD80 / CTLA-4 are present on the cell surface separately from MHC.[7].CadherinBoth the molecule / KLRG1 molecule are different molecules from PD-L1 / PD-1 and CD80 / CTLA-4, which are generally regarded as immune checkpoint molecules. (Note that the general cell / T cell format used in this chapter is not a general format, so be careful when using it in explanations to third parties.)

Mechanism of action

At least in the T cells of vertebrates such as humans, there are some parts in the T cells to which the factors of their own cells can bind so as not to attack the cells of the living individual (other than the T cells). It's like a key and a keyhole.In the case of humans, PD-1, CTLA-4, LAG-3, Tim-3, KLRG1 and the like of T cells are known as factors on the keyhole side of the T cell side where only their own cells can bind. ing.

On the other hand, general cells on the key side have factors such as PD-L1, CD80, MHC, and E-cadherin, which bind to molecules on the key hole side of T cells, for example, PD-L1 binds to PD-1. As a result, general cells are immune to attack from T cells, and such a mechanism is an immune checkpoint.In other words, it is a mechanism to confirm whether the cell with which the T cell is in contact is a companion.

However, since cancer cells are also autologous cells, they have molecules such as PD-L1, so cancer cells abuse this mechanism and are the key side of cancer cells. Factors (such as PD-L1) also bind to T cells, allowing cancer cells to escape the attack of immune cells.

Immune checkpoint inhibitors block the binding of molecules that switch immune checkpoints in some way, making it impossible for cancer cell factors to bind to the keyholes of T cells. It is a drug that alters cells to attack many cells indiscriminately, including cancer cells.Therefore, as a side effect, PD-L1 and the like possessed by normal general cells cannot bind to PD-1 of T cells, and it is said that there is a risk of developing autoimmune diseases.

Immune checkpoints are excessiveImmune responseSuppress,Autoimmune diseaseIt has a function to suppress the occurrence of such.Immune checkpoints involved in this mechanismproteinas,Dendritic cellsEtc.Antigen presenting cellsResponds to the receptor CD80 / 86 CTLA-4,Tumor cellsSurface PD-L1 LigandRespond to PD 1 Etc. are known[5]..Both proteins are from T cellsCell membranePresent on the surface.Against these proteinsInhibitor antibodyIs an immune checkpoint inhibitor.By administering such an immune checkpoint inhibitor, the immunosuppression of T cells is released and the antitumor immune response is enhanced.[8].

Side effects

When nivolumab was put into practical use, immune checkpoint inhibitors were thought to only enhance the immune function of the human body and have fewer or fewer side effects than conventional chemotherapy with anticancer drugs.In fact, the side effects themselves are few, but on the other hand, it has been reported that there are patients who exhibit symptoms not seen with conventional chemotherapy.For example acuteType 1 diabetesAnd severe skin symptoms,Toxic epidermal necrolysis(Toxic Epidermal Necrolysis: TEN),Mucocutaneous ocular syndrome(Stevens-Johnson Syndrome: SJS).They areImmune-related adverse eventsIt is called (immune-related Adverse Events: irAE) and is a precaution when using immune checkpoint inhibitors.Some researchers consider it an immune-related adverse effect as a side effect rather than an adverse event.

As a mechanism of action of irAE, it is considered that an immune checkpoint inhibitor reduces the suppressive action of the immune system, resulting in an autoimmune disease action on the histiocytes of the patient. Reported as irAE extends to the whole body such as the skin, nervous system, heart, lungs, liver, endocrine organs, and gastrointestinal tract, and when irAE develops, administration of immunosuppressive agents such as steroids or infliximab is required. , Immune checkpoint inhibitors need to be withdrawn.

Types

As of November 2018, the following immune checkpoint inhibitors have been approved in Japan.The indications for each drug are being expanded as needed after obtaining approval.

Anti-CTLA-4 antibody

Anti-PD-1 antibody

Anti-PD-L1 antibody

Related item

footnote

  1. ^ a b Kanagawa Cancer Center Clinical Research Institute
  2. ^ NHK close-up gendai
  3. ^ Nikkei Medical 2014.9
  4. ^ Japan Agency for Medical Research and Development, Press Release "Elucidation of the mechanism by which cancer cells escape from immunity-Expected to be applied to predict the effect of immune checkpoint inhibitors-"
  5. ^ a b Immune Checkpoint Inhibitors: Biokeywords | Experimental Medicine online: Yodosha
  6. ^ Masayuki Miyasaka Edited by "Standard Immunology", Igaku-Shoin, February 2016, 2, 1rd Edition, 3nd Edition, Figure 2-38, page 2
  7. ^ Edited by Masayuki Miyasaka et al., "Standard Immunology", Igaku-Shoin, February 2016, 2, 1rd edition, 3nd edition, page 2, drawing at the top of the page
  8. ^ Daisuke Sugiyama, Hiroyoshi Nishikawa "Cancer immunotherapy: From basic research to clinical application"Regional Fusion Review," Volume 4, 2015, e005, two:10.7875 / leading.author.4.e005.

 

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