Immune cells could help kill cancer cells, finds study
In a new study, researchers from UCL Cancer Institute have found that a subset of immune cells are capable of killing cancer cells when they are activated. This could lay the foundation stone for effective anti-cancer therapies believe the researchers.
The study titled, "Regulatory T cells restrain Interleukin-2 and Blimp-1-Dependent acquisition of cytotoxic function by CD4+ T cells" was published in the latest issue of the journal Immunity on the 7th of January 2020.
Activation of immune cells upon immunotherapy
This study was led by Professors Sergio Quezada and Karl Peggs, who had conducted previous research on the same theory, have found that when the immune system is subjected to immunotherapy, some of the cells are activated.
These activated CD4+ T cells were initially thought to be helper cells and regulate the immune cells. When activated, these cells have been found to become killer cells and directly kill the cancer cells. This has been proven in animal studies on lab mice, the authors wrote.
Study results
The study funded by the Cancer Research UK was an in-depth analysis of what happened at the cellular level, in order to see what the immune cells do to cancer cells. The cellular mechanisms of these activities have been outlined in this research.
Results revealed that in the T cells, a growth factor called Interleukin 2 (IL-2) was the main factor behind the cytotoxic or cell killing activities. This was aided by the 'transcription factor' Blimp-1. Both of these factors are responsible for starting the killer activities of the CD4+ T cells within the cancers.
We knew these immune cells had the ability to proactively kill cancer cells with incredible potency, but to maximize their potential, we needed to know how this mechanism was activated. Our discovery provides the evidence and rationale for utilising Blimp-1 to maximise the anti-tumour activity of CD4+ T cells. Work is now underway in our lab to develop new personalized cell therapies where the activity of Blimp-1 can be maxed up to drive potent tumor control." Professor Sergio Quezada, UCL Cancer Institute
The team explained that T-type lymphocytes are generally the attacker cells of the immune system, killing infected cells around the body. These cells, however, are normally incapable of killing cancer cells because cancer cells are made up of the body's own cells. When these T cells are activated using immunotherapy, they are modified so that they can attack cancer cells. The actual challenge of immunotherapy thus lies in activating the T cells, explained the researchers.
Mouse models of cancer
The team used transplantable and autochthonous mouse models of cancer, wrote the researchers. They explained, "CD4+ T cells play a key role in the regulation of immune responses to self and foreign antigens, differentiating into various subsets of helper and regulatory T cells and instructing the function of CD8+ T cells, NK cells and macrophages.
Nonetheless, little is still know about the biology of tumour-reactive CD4+ T cells during tumour progression and cancer immunotherapy. Most importantly, we recently demonstrated that tumor-reactive CD4+ T cells can also acquire granzyme-dependent cytotoxic activity and directly target and kill tumor cells in vivo." This study was thus undertaken to see how the functions of these tumor-reactive CD4 T cells could be controlled and modified.
The team concluded that the tumor-infiltrating CD4 + T cells demonstrate T helper and cytotoxic features. Further Treg (T regulatory cells) cells reduce the availability of IL-2, which is essential for cytotoxic features of the T cells.
They write that T-bet is required for Interferon Gamma (IFN-γ) expression within the CD4+ cells. On the one hand, Blimp-1 is required for GzmB (granzyme B) expression in the T cells when stimulated by IL2, but T-bet is not needed for GzmB expression.
Applying these results to therapies
Professor Karl Peggs said in his statement, "Cellular therapies have only recently entered the mainstream in terms of clinical application. Much remains unknown regarding how best to optimise these therapies, particularly to enable better activity in solid organ cancers. Our findings broaden our understanding of the regulators of T cell differentiation, illuminating new elements that might be targeted to enhance therapeutic efficacy."
From Cancer Research UK, Dr. Emily Farthing, research information manager said in her statement, "Research like this helps scientists better understand the intricacies of our immune system and how it can be utilized to kill cancer cells. This work in the lab adds to growing evidence for the potential of immunotherapy and will hopefully lead to the development of more effective treatments for people affected by cancer."
Major genetic study provides most comprehensive map of breast cancer risk variants to date
A major international study of the genetics of breast cancer has identified more than 350 DNA 'errors' that increase an individual's risk of developing the disease. The scientists involved say these errors may influence as many as 190 genes.
The results, published today in the journal Nature Genetics, provide the most comprehensive map of breast cancer risk variants to date. The researchers involved, from over 450 departments and institutions worldwide, say the findings will help provide the most detailed picture yet of how differences in our DNA put some women at greater risk than others of developing the disease.
The majority of the DNA is identical between individuals, but there are some differences, known as genetic variants, and these changes can have a profound effect, increasing an individual's susceptibility to disease.
Our DNA - the blueprint for the human body - contains between 20,000-25,000 genes. Many of these code for proteins, the building blocks that make up the human body. Genetic variants can be located within genes, altering the protein. However, most of genetic variants are located outside genes, sometimes regulating the function of genes, turning their 'volume' up or down or even off. Finding which gene is targeted by these variants is not straightforward.
Most diseases are complex, polygenetic diseases - in other words, no single genetic variant or gene causes the disease, but rather the combination of a number of them act together to increase the likelihood that an individual will develop a particular disease. Breast cancer is one such disease.
Previous genome-wide association studies (GWAS), which involve comparing the DNA of patients against that of healthy controls, have found around 150 regions of the genome that clearly affect breast cancer risk. Within these regions, researchers know there are one or more genetic changes that affect the risk of developing cancer, but rarely are they able to pinpoint the specific variants or genes involved. Fine-mapping studies, such as this one, allow scientists to narrow down which variants contributing to the disease, how they might work and predict which are the genes involved.
"We know from previous studies that variants across our DNA contribute towards breast cancer risk, but only rarely have scientists have been able to identify exactly which genes are involved," said Dr Laura Fachal from the Wellcome Sanger Institute. "We need this information as it gives us a better clue to what is driving the disease and hence how we might treat or even prevent it."
In this new study, researchers from hundreds of institutions worldwide collaborated to compare the DNA of 110,000 breast cancer patients against that of some 90,000 healthy controls. By looking in much closer detail than was previously possibly, they identified 352 risk variants. It is not yet clear exactly how many genes these target, but the researchers have identified 191 genes with reasonable confidence; less than one in five of these had been previously recognized.
This incredible haul of newly-discovered breast cancer genes provides us with many more genes to work on, most of which have not been studied before. It will help us build up a much more detailed picture of how breast cancer arises and develops. But the sheer number of genes now known to play a role emphasizes how complex the disease is." Dr. Alison Dunning, University of Cambridge.
The study titled, "Regulatory T cells restrain Interleukin-2 and Blimp-1-Dependent acquisition of cytotoxic function by CD4+ T cells" was published in the latest issue of the journal Immunity on the 7th of January 2020.
Activation of immune cells upon immunotherapy
This study was led by Professors Sergio Quezada and Karl Peggs, who had conducted previous research on the same theory, have found that when the immune system is subjected to immunotherapy, some of the cells are activated.
These activated CD4+ T cells were initially thought to be helper cells and regulate the immune cells. When activated, these cells have been found to become killer cells and directly kill the cancer cells. This has been proven in animal studies on lab mice, the authors wrote.
Study results
The study funded by the Cancer Research UK was an in-depth analysis of what happened at the cellular level, in order to see what the immune cells do to cancer cells. The cellular mechanisms of these activities have been outlined in this research.
Results revealed that in the T cells, a growth factor called Interleukin 2 (IL-2) was the main factor behind the cytotoxic or cell killing activities. This was aided by the 'transcription factor' Blimp-1. Both of these factors are responsible for starting the killer activities of the CD4+ T cells within the cancers.
We knew these immune cells had the ability to proactively kill cancer cells with incredible potency, but to maximize their potential, we needed to know how this mechanism was activated. Our discovery provides the evidence and rationale for utilising Blimp-1 to maximise the anti-tumour activity of CD4+ T cells. Work is now underway in our lab to develop new personalized cell therapies where the activity of Blimp-1 can be maxed up to drive potent tumor control." Professor Sergio Quezada, UCL Cancer Institute
The team explained that T-type lymphocytes are generally the attacker cells of the immune system, killing infected cells around the body. These cells, however, are normally incapable of killing cancer cells because cancer cells are made up of the body's own cells. When these T cells are activated using immunotherapy, they are modified so that they can attack cancer cells. The actual challenge of immunotherapy thus lies in activating the T cells, explained the researchers.
Mouse models of cancer
The team used transplantable and autochthonous mouse models of cancer, wrote the researchers. They explained, "CD4+ T cells play a key role in the regulation of immune responses to self and foreign antigens, differentiating into various subsets of helper and regulatory T cells and instructing the function of CD8+ T cells, NK cells and macrophages.
Nonetheless, little is still know about the biology of tumour-reactive CD4+ T cells during tumour progression and cancer immunotherapy. Most importantly, we recently demonstrated that tumor-reactive CD4+ T cells can also acquire granzyme-dependent cytotoxic activity and directly target and kill tumor cells in vivo." This study was thus undertaken to see how the functions of these tumor-reactive CD4 T cells could be controlled and modified.
The team concluded that the tumor-infiltrating CD4 + T cells demonstrate T helper and cytotoxic features. Further Treg (T regulatory cells) cells reduce the availability of IL-2, which is essential for cytotoxic features of the T cells.
They write that T-bet is required for Interferon Gamma (IFN-γ) expression within the CD4+ cells. On the one hand, Blimp-1 is required for GzmB (granzyme B) expression in the T cells when stimulated by IL2, but T-bet is not needed for GzmB expression.
Applying these results to therapies
Professor Karl Peggs said in his statement, "Cellular therapies have only recently entered the mainstream in terms of clinical application. Much remains unknown regarding how best to optimise these therapies, particularly to enable better activity in solid organ cancers. Our findings broaden our understanding of the regulators of T cell differentiation, illuminating new elements that might be targeted to enhance therapeutic efficacy."
From Cancer Research UK, Dr. Emily Farthing, research information manager said in her statement, "Research like this helps scientists better understand the intricacies of our immune system and how it can be utilized to kill cancer cells. This work in the lab adds to growing evidence for the potential of immunotherapy and will hopefully lead to the development of more effective treatments for people affected by cancer."
Major genetic study provides most comprehensive map of breast cancer risk variants to date
A major international study of the genetics of breast cancer has identified more than 350 DNA 'errors' that increase an individual's risk of developing the disease. The scientists involved say these errors may influence as many as 190 genes.
The results, published today in the journal Nature Genetics, provide the most comprehensive map of breast cancer risk variants to date. The researchers involved, from over 450 departments and institutions worldwide, say the findings will help provide the most detailed picture yet of how differences in our DNA put some women at greater risk than others of developing the disease.
The majority of the DNA is identical between individuals, but there are some differences, known as genetic variants, and these changes can have a profound effect, increasing an individual's susceptibility to disease.
Our DNA - the blueprint for the human body - contains between 20,000-25,000 genes. Many of these code for proteins, the building blocks that make up the human body. Genetic variants can be located within genes, altering the protein. However, most of genetic variants are located outside genes, sometimes regulating the function of genes, turning their 'volume' up or down or even off. Finding which gene is targeted by these variants is not straightforward.
Most diseases are complex, polygenetic diseases - in other words, no single genetic variant or gene causes the disease, but rather the combination of a number of them act together to increase the likelihood that an individual will develop a particular disease. Breast cancer is one such disease.
Previous genome-wide association studies (GWAS), which involve comparing the DNA of patients against that of healthy controls, have found around 150 regions of the genome that clearly affect breast cancer risk. Within these regions, researchers know there are one or more genetic changes that affect the risk of developing cancer, but rarely are they able to pinpoint the specific variants or genes involved. Fine-mapping studies, such as this one, allow scientists to narrow down which variants contributing to the disease, how they might work and predict which are the genes involved.
"We know from previous studies that variants across our DNA contribute towards breast cancer risk, but only rarely have scientists have been able to identify exactly which genes are involved," said Dr Laura Fachal from the Wellcome Sanger Institute. "We need this information as it gives us a better clue to what is driving the disease and hence how we might treat or even prevent it."
In this new study, researchers from hundreds of institutions worldwide collaborated to compare the DNA of 110,000 breast cancer patients against that of some 90,000 healthy controls. By looking in much closer detail than was previously possibly, they identified 352 risk variants. It is not yet clear exactly how many genes these target, but the researchers have identified 191 genes with reasonable confidence; less than one in five of these had been previously recognized.
This incredible haul of newly-discovered breast cancer genes provides us with many more genes to work on, most of which have not been studied before. It will help us build up a much more detailed picture of how breast cancer arises and develops. But the sheer number of genes now known to play a role emphasizes how complex the disease is." Dr. Alison Dunning, University of Cambridge.