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This article was originally written by Translational Medicine.
Please indicate the source.
Author: Ashley Introduction: Cancer immunotherapy often fails because most cancers have very few T cells, suggesting that cancer can inhibit T cell infiltration
.
Recent studies have identified an immune-inactivating pathway that provides a promising new treatment for pancreatic, breast and colorectal cancers
.
Our immune system has the potential to find and destroy cancer cells
.
But cancer cells can be smart and develop tricks to evade the immune system
.
Cold Spring Harbor Laboratory Professor Douglas Fearon and his former postdoc ZhiKai Wang discovered one such trick
.
Cancer cells weave inactivating signals into a protective layer that keeps out T cells that would otherwise kill them
.
This immune inactivation pathway offers a promising new treatment for pancreatic, breast and colorectal cancers
.
T cells patrol the body in search of cancer and pathogens
.
If they or their immune system teammates find an invader, the T cells will attack
.
Now Wang, a researcher at the China University of Science and Technology in Hefei, has found that this mobilization is disabled by a combination of three proteins woven into the protective membrane surrounding cancer cells: a signal that normally attracts T cells called CXCL12, and a signal called KRT19.
The filament, along with a protein called TGM2, fuses the first two proteins together
.
The scientists used gene editing to turn off the production of KRT19 or TGM2 in mouse pancreatic tumors
.
Without KRT19 or TGM2, cancer cells lost CXCL12-KRT19 protection, T cells were able to infiltrate and attack, and pancreatic tumors shrank or disappeared
.
Why does this coat protein repel T cells in tumors? "It's a bit counterintuitive, because CXCL12 is a chemokine (chemoattractant) that attracts immune cells," Wang said
.
But we found that CXCL12, which is found in abnormally high concentrations on the surface of cancer cells, has the opposite effect, making T cells Can't move
.
" CXCL12 normally functions as a single protein
.
But at high concentrations on the cancer cell surface, the protein forms a complex with KRT19, forming a branch-like network
.
This network significantly reduced T cell motility
.
The study, published in Proceedings of the National Academies of Sciences of the United States of America (PNAS), is titled "Carcinomas assemble a filamentous CXCL12–keratin-19 coating that suppresses T cell–mediated immune attack
.
"
In a previous small clinical study in pancreatic cancer patients, Fearon and his collaborators showed that the drug plerixafor, a CXCL12 receptor blocker, increased T cell infiltration into the patients' pancreatic tumor tissue
.
The current study shows why this immunotherapy effect occurs
.
Fearon and Wang hope that CXCL12 and KRT19 will provide new therapeutic targets that improve the immune system's chances of killing cancer cells
.
Reference: https://medicalxpress.
com/news/2022-02-pancreatic-tumors-defenses.
html Note: This article aims to introduce the progress of medical research and cannot be used as a reference for treatment plans
.
For health guidance, please go to a regular hospital for treatment
.
Recommendation·Events The First Yangtze River Delta Single Cell Omics Technology Application Forum [Webinar] Synthetic Biology Innovation and Development Popularity·Articles Stem Cell Research [Nature Sub-Journal] Using Stem Cells to Regenerate the Heart! Gene sequencing [Nature sub-journal] Analysis of 2658 complete DNA sequences - providing new clues for cancer mutations Cancer research [Science sub-journal] Will "lactic acid" help cancer cells? Studies have found that specific enzymes can fight it! Single-cell omics [guest announcement] The first Yangtze River Delta single-cell omics technology forum will be held in Shanghai in early March.
The second issue of precision medicine "Precision Medicine" is coming! What kind of sparks can CAR-T and MRD collide with? Big coffee gathered to explain to you! Detection and diagnosis [Nature sub-journal] Fudan University Wei Dacheng's team and academician Liu Yunqi have developed an ultra-high-sensitivity detection portable device that can produce results in 4 minutes! PCR detection or be replaced!
Please indicate the source.
Author: Ashley Introduction: Cancer immunotherapy often fails because most cancers have very few T cells, suggesting that cancer can inhibit T cell infiltration
.
Recent studies have identified an immune-inactivating pathway that provides a promising new treatment for pancreatic, breast and colorectal cancers
.
Our immune system has the potential to find and destroy cancer cells
.
But cancer cells can be smart and develop tricks to evade the immune system
.
Cold Spring Harbor Laboratory Professor Douglas Fearon and his former postdoc ZhiKai Wang discovered one such trick
.
Cancer cells weave inactivating signals into a protective layer that keeps out T cells that would otherwise kill them
.
This immune inactivation pathway offers a promising new treatment for pancreatic, breast and colorectal cancers
.
T cells patrol the body in search of cancer and pathogens
.
If they or their immune system teammates find an invader, the T cells will attack
.
Now Wang, a researcher at the China University of Science and Technology in Hefei, has found that this mobilization is disabled by a combination of three proteins woven into the protective membrane surrounding cancer cells: a signal that normally attracts T cells called CXCL12, and a signal called KRT19.
The filament, along with a protein called TGM2, fuses the first two proteins together
.
The scientists used gene editing to turn off the production of KRT19 or TGM2 in mouse pancreatic tumors
.
Without KRT19 or TGM2, cancer cells lost CXCL12-KRT19 protection, T cells were able to infiltrate and attack, and pancreatic tumors shrank or disappeared
.
Why does this coat protein repel T cells in tumors? "It's a bit counterintuitive, because CXCL12 is a chemokine (chemoattractant) that attracts immune cells," Wang said
.
But we found that CXCL12, which is found in abnormally high concentrations on the surface of cancer cells, has the opposite effect, making T cells Can't move
.
" CXCL12 normally functions as a single protein
.
But at high concentrations on the cancer cell surface, the protein forms a complex with KRT19, forming a branch-like network
.
This network significantly reduced T cell motility
.
The study, published in Proceedings of the National Academies of Sciences of the United States of America (PNAS), is titled "Carcinomas assemble a filamentous CXCL12–keratin-19 coating that suppresses T cell–mediated immune attack
.
"
In a previous small clinical study in pancreatic cancer patients, Fearon and his collaborators showed that the drug plerixafor, a CXCL12 receptor blocker, increased T cell infiltration into the patients' pancreatic tumor tissue
.
The current study shows why this immunotherapy effect occurs
.
Fearon and Wang hope that CXCL12 and KRT19 will provide new therapeutic targets that improve the immune system's chances of killing cancer cells
.
Reference: https://medicalxpress.
com/news/2022-02-pancreatic-tumors-defenses.
html Note: This article aims to introduce the progress of medical research and cannot be used as a reference for treatment plans
.
For health guidance, please go to a regular hospital for treatment
.
Recommendation·Events The First Yangtze River Delta Single Cell Omics Technology Application Forum [Webinar] Synthetic Biology Innovation and Development Popularity·Articles Stem Cell Research [Nature Sub-Journal] Using Stem Cells to Regenerate the Heart! Gene sequencing [Nature sub-journal] Analysis of 2658 complete DNA sequences - providing new clues for cancer mutations Cancer research [Science sub-journal] Will "lactic acid" help cancer cells? Studies have found that specific enzymes can fight it! Single-cell omics [guest announcement] The first Yangtze River Delta single-cell omics technology forum will be held in Shanghai in early March.
The second issue of precision medicine "Precision Medicine" is coming! What kind of sparks can CAR-T and MRD collide with? Big coffee gathered to explain to you! Detection and diagnosis [Nature sub-journal] Fudan University Wei Dacheng's team and academician Liu Yunqi have developed an ultra-high-sensitivity detection portable device that can produce results in 4 minutes! PCR detection or be replaced!
