User login
Credit: Volker Brinkmann
New research has revealed distinct subpopulations of neutrophils that have conflicting functions when it comes to cancer.
Investigators identified a population of “normal,” high-density neutrophils (HDNs) that have anti-tumor properties and a population of low-density
neutrophils (LDNs) that exhibit pro-tumor activity.
They also found that the ratio of HDNs to LDNs determines whether the neutrophils have a pro- or anti-cancer effect overall.
This suggests we may be able to fight cancers by increasing the proportion of the anti-tumor HDNs while limiting the pro-tumor LDNs, according to Zvika Granot, PhD, of Hebrew University Medical School in Jerusalem, Israel.
“The novel distinction between harmful and beneficial neutrophils opens up new diagnostic and therapeutic opportunities,” Dr Granot said. “We are currently evaluating the effects of boosting the helpful anti-tumor neutrophil population, while limiting the tumor-promoting neutrophil population, on progression of the disease. If successful, this therapeutic strategy may take us closer to developing effective new therapies for cancer.”
Dr Granot and his colleagues described their discovery of LDNs and HDNs in Cell Reports.
The investigators found that LDNs were rare in healthy control subjects, but they accumulated in tumor-bearing mice and in cancer patients. HDNs exhibited cytotoxicity toward cancer cells and retarded tumor growth, but LDNs did not.
LDNs had impaired neutrophil function and immunosuppressive properties. They consisted of immature myeloid-derived suppressor cells and mature cells that were derived from HDNs.
HDNs transformed into LDNs in a TGF-β-dependent fashion, losing their anti-tumor properties and gaining immunosuppressive properties.
In the early stages of cancer development, HDNs prevailed. But as cancer progressed, the LDNs took over, and the overall neutrophil contribution became tumor-promoting.
The investigators noted that the expansion of LDNs was a relatively late event. So although these neutrophils likely contribute to tumor growth and progression, it’s less likely that they contribute to tumor initiation.
Regardless, this research challenges the concept that mature neutrophils are limited in their ability to change. It shows that neutrophils are not a homogeneous population of cells and may consist of multiple subtypes. And it provides a mechanistic explanation for the controversy surrounding neutrophil function in cancer. 
Credit: Volker Brinkmann
New research has revealed distinct subpopulations of neutrophils that have conflicting functions when it comes to cancer.
Investigators identified a population of “normal,” high-density neutrophils (HDNs) that have anti-tumor properties and a population of low-density
neutrophils (LDNs) that exhibit pro-tumor activity.
They also found that the ratio of HDNs to LDNs determines whether the neutrophils have a pro- or anti-cancer effect overall.
This suggests we may be able to fight cancers by increasing the proportion of the anti-tumor HDNs while limiting the pro-tumor LDNs, according to Zvika Granot, PhD, of Hebrew University Medical School in Jerusalem, Israel.
“The novel distinction between harmful and beneficial neutrophils opens up new diagnostic and therapeutic opportunities,” Dr Granot said. “We are currently evaluating the effects of boosting the helpful anti-tumor neutrophil population, while limiting the tumor-promoting neutrophil population, on progression of the disease. If successful, this therapeutic strategy may take us closer to developing effective new therapies for cancer.”
Dr Granot and his colleagues described their discovery of LDNs and HDNs in Cell Reports.
The investigators found that LDNs were rare in healthy control subjects, but they accumulated in tumor-bearing mice and in cancer patients. HDNs exhibited cytotoxicity toward cancer cells and retarded tumor growth, but LDNs did not.
LDNs had impaired neutrophil function and immunosuppressive properties. They consisted of immature myeloid-derived suppressor cells and mature cells that were derived from HDNs.
HDNs transformed into LDNs in a TGF-β-dependent fashion, losing their anti-tumor properties and gaining immunosuppressive properties.
In the early stages of cancer development, HDNs prevailed. But as cancer progressed, the LDNs took over, and the overall neutrophil contribution became tumor-promoting.
The investigators noted that the expansion of LDNs was a relatively late event. So although these neutrophils likely contribute to tumor growth and progression, it’s less likely that they contribute to tumor initiation.
Regardless, this research challenges the concept that mature neutrophils are limited in their ability to change. It shows that neutrophils are not a homogeneous population of cells and may consist of multiple subtypes. And it provides a mechanistic explanation for the controversy surrounding neutrophil function in cancer.
Credit: Volker Brinkmann
New research has revealed distinct subpopulations of neutrophils that have conflicting functions when it comes to cancer.
Investigators identified a population of “normal,” high-density neutrophils (HDNs) that have anti-tumor properties and a population of low-density
neutrophils (LDNs) that exhibit pro-tumor activity.
They also found that the ratio of HDNs to LDNs determines whether the neutrophils have a pro- or anti-cancer effect overall.
This suggests we may be able to fight cancers by increasing the proportion of the anti-tumor HDNs while limiting the pro-tumor LDNs, according to Zvika Granot, PhD, of Hebrew University Medical School in Jerusalem, Israel.
“The novel distinction between harmful and beneficial neutrophils opens up new diagnostic and therapeutic opportunities,” Dr Granot said. “We are currently evaluating the effects of boosting the helpful anti-tumor neutrophil population, while limiting the tumor-promoting neutrophil population, on progression of the disease. If successful, this therapeutic strategy may take us closer to developing effective new therapies for cancer.”
Dr Granot and his colleagues described their discovery of LDNs and HDNs in Cell Reports.
The investigators found that LDNs were rare in healthy control subjects, but they accumulated in tumor-bearing mice and in cancer patients. HDNs exhibited cytotoxicity toward cancer cells and retarded tumor growth, but LDNs did not.
LDNs had impaired neutrophil function and immunosuppressive properties. They consisted of immature myeloid-derived suppressor cells and mature cells that were derived from HDNs.
HDNs transformed into LDNs in a TGF-β-dependent fashion, losing their anti-tumor properties and gaining immunosuppressive properties.
In the early stages of cancer development, HDNs prevailed. But as cancer progressed, the LDNs took over, and the overall neutrophil contribution became tumor-promoting.
The investigators noted that the expansion of LDNs was a relatively late event. So although these neutrophils likely contribute to tumor growth and progression, it’s less likely that they contribute to tumor initiation.
Regardless, this research challenges the concept that mature neutrophils are limited in their ability to change. It shows that neutrophils are not a homogeneous population of cells and may consist of multiple subtypes. And it provides a mechanistic explanation for the controversy surrounding neutrophil function in cancer.