Thanks for "science", we have another HD blockbuster this week!
Let's start with a moving picture to feast our eyes~
What is this? This is the first-hand on-site information sent by the front line of T cell anti-cancer ~t cell a personal explosion, the cancer cell instantly died ~ the death sticker is true.
T cells kill cancer cells by "close body poisoning". T cells will cling to cancer cells, release perforin, and "open holes" in the cell membrane of cancer cells, and then send granzyme into cancer cells to realize instant explosion.
Of course, cancer cells are not completely passively waiting to die. A new study published in the journal Science this week used advanced low-temperature imaging technology and focused ion beam scanning electron microscope (FIB-SEM) to reproduce the most subtle battlefield details of this anti-cancer war and the weak resistance of cancer cells at a resolution of 8nm [1]. This paper is also the cover study of this week's science. The corresponding authors are IRA Mellman and Alex T. Ritter from Genentech.
How can cancer cells resist? With an idea of what is missing and what is needed, T cells have opened holes in the cell membrane. Can we fill the holes before they are killed by granzyme?
Don't say, it's really basic.
There is a protein called endosomal sorting complex (ESCRT) required for transport, which is involved in cell membrane remodeling and damage repair. Previous studies have found that ESCRT can repair the pores on the plasma membrane caused by bacterial porotoxin, mechanical damage and laser [2,3].
Well, I think you should realize at this time that this study is to verify that ESCRT is also involved in the repair of membrane damage caused by T-cell perforin, and it should be verified successfully
So let's stop talking nonsense. Let me explain this interesting mechanism directly to you.
Let's look at the picture first. When perforin causes perforin pore on the surface of cancer cells, ESCRT will gather at the site of perforation.
Under the action of ESCRT, the damaged and perforated cell membrane formed buds, and then "boo" fell down (this step is questionable)! Just break the membrane like this. We are a good cell again.
However, this study only observed some phenomena, which can not be said to nail the whole process. Combined with the results of previous studies, it is basically like this. In the study, it was also observed that cancer cells were more sensitive to perforin and granzyme after ESCRT knockout.
After ESCRT knockout, cancer cells are more sensitive to perforin / granzyme killing
In addition, ESCRT will not be the only means for cancer cells to resist. Researchers believe that cancer cells may also engage in repair engineering by swallowing the perforated part of the membrane and secreting lysosomes. These need further research.
Then it's all about watching movies~
In the following picture, magenta is T cells, gray / green is cancer cells, and bright orange red is a high concentration dye propidium iodide (PI), which can rapidly diffuse through the perforation on the membrane and bind nucleic acids in the cytoplasm and nucleus.
So where is ESCRT?
Look here ~ have you seen a little bright green between T cells and cancer cells? That is the fluorescent protein labeled ESCRT. Within 30 to 60 seconds after propidium iodide flowed in, ESCRT arrived at the perforation site.
Here is an exploded view.
The researchers also recorded footage of ESCRT sticking to T cells.
The researchers speculated that this should be the detached membrane fragment containing ESCRT, because it contains the ligand of T cell receptor, so it adheres to T cells.
Most importantly, in order to understand what happened between T cells and cancer cells, researchers also used low-temperature fluorescence imaging to fix the moment when the two sides fought, and used electron microscopy to reconstruct the 3D model.
Take a look at this exquisite detail.
Even cell substructures can be reduced one by one.
However, in order to put it on, this picture has been compressed a lot (hate).
Reference material:
[1] https://www.science.org/doi/10.1126/science.abl3855
[2]A. J. Jimenez, P. Maiuri, J. Lafaurie-Janvore, S. Divoux, M. Piel, F. Perez, ESCRT machinery is required for plasma membrane repair. Science343, 1247136 (2014).
[3]L. L. Scheffer, S. C. Sreetama, N. Sharma, S. Medikayala, K. J. Brown, A. Defour, J. K. Jaiswal, Mechanism of Ca2+-triggered ESCRT assembly and regulation of cell membrane repair. Nat. Commun. 5, 5646 (2014).
Author Dai Siyu
Source: singularity
https://mp.weixin.qq.com/s/zzSvBVRchtCByeMNSZx-fw
