Health scan: Not all neutrophils are created equal in fighting cancer

March 8, 2015 00:21
4 minute read.

Man lying in a hospital bed at Hadassah University Medical Center in Jerusalem’s Ein Kerem [illustrative].. (photo credit: MARC ISRAEL SELLEM/THE JERUSALEM POST)

The most common form of white blood cells – called neutrophils – contain many different subtypes, of which some fight the development of cancer and others promote its progression. New Hebrew University research could help pave the way to new therapies that fight cancer by increasing anti-tumor neutrophils while limiting pro-tumor neutrophils.

Traditionally, cancer research has focused on trying to identify aspects of cancer development that can be exploited therapeutically with chemotherapy and radiation.

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In the last decade, new approaches to cancer have involved activating the immune system against cancer cells without harming healthy tissue, which has proven effective in a limited range of patients.

However, in recent years it became clear that in addition to the cancer cells themselves, healthy cells surrounding a tumor play a critical role in promoting cancer development.

These cells, which provide a supportive environment that promotes tumor growth and allows it to spread, are potential targets for new cancer therapies.

The role of neutrophils, which comprise between half to 70 percent of all white blood cells, remains controversial.

While neutrophils are traditionally associated with inflammation and fighting infections, accumulating data suggest they also play an important role in tumor biology.

In a just-published study in the journal Cell Reports, Dr. Zvika Granot and Dr. Zvi Fridlender scientists working with mouse tumors and human blood samples challenge the concept that mature neutrophils are limited in their ability to change and take on new characteristics. They also show that in contrast to current perceptions, neutrophils are not a homogeneous population of cells but rather consist of multiple subtypes.

The researchers found that while some neutrophils have anti-tumor properties, others in fact promote tumor progression. They also showed that in early stages of the disease, tumor-limiting neutrophils prevail. However, as cancer progresses, the tumor-promoting neutrophil subpopulation that promotes tumor growth outcompete the tumor-limiting neutrophil subpopulation, and the overall neutrophil contribution becomes tumor-promoting.

“The novel distinction between harmful and beneficial neutrophils opens up new diagnostic and therapeutic opportunities,” 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.”

SMOKING AND PROSTATE CANCER Among patients with prostate cancer, those who smoke have increased risks of experiencing side effects from treatment and of developing recurrences or even dying from prostate cancer. The findings, just published in BJU International, suggest that smoking may negatively affect the health outcomes of patients with prostate cancer contribute to complications related to their care.

Several studies have demonstrated links between cigarette smoking and prostate cancer. To better understand the influence of smoking on prostate cancer progression and treatment, radiation oncology Prof. Michael Zelefsky of New York’s Memorial Sloan Kettering Cancer and colleagues studied 2,358 patients who underwent external beam radiotherapy for prostate cancer between 1988 and 2005. Of these, 2,156 had a history of smoking. Patients were classified as never smokers, current smokers, former smokers, and current smoking unknown.

Over a median follow-up of nearly eight years, patients who were current smokers had a 40% increased risk of cancer relapse, as well as more than double the risk of cancer spread and cancer-related death, compared with patients who were never smokers. In addition, current and former smokers had a higher likelihood of experiencing side effects such as urinary toxicity that were related to radiotherapy. Examples of urinary toxicity include urinary retention, urinary incontinence and bladder hemorrhage.

“Less optimal tumor control outcomes among smokers could possibly be explained by the influence of less oxygen concentration within the treated tumors among smokers, which is known to lead to less sensitivity of the cells being killed off by radiation treatments,” Zelefsky noted. “Our findings point to the importance of physicians counseling their patients regarding the potential harms of smoking interfering with the efficacy of therapies and for increased risks of side effects.”

JERUSALEM NEONATOLOGIST NAMED JOURNAL EDITOR Politics sometimes thwarts capable Israelis from getting international recognition and positions – even in the field of medical research. But fortunately, highly skilled doctors can be appointed editors of foreign medical journals; the latest case in point is Prof. Francis Mimouni, chief of neonatology at Jerusalem’s Shaare Zedek Medical Center, who has just been named editor of the prestigious Journal of Perinatology, part of the Nature group and the official journal of American perinatologists. The articles deal with clinical, professional, political, administrative and educational aspects of the field, and the scope of the journal reflects the multidisciplinary nature of the subject, including maternal and fetal medicine, the neonatal period and the follow-up of the infant and child.

“It is a great honor, especially at a time when [Israel’s] status in the world is not outstanding. Of all the 30 editorial board members, only two are not American residents,” said Mimouni.

The journal has the highest “impact factor” (measured by how often it is quoted by experts) in this field. Recently, a textbook for medical students co-edited by Mimouni on pharmacology and nutrition of newborns, including premature babies, was published. “We noticed that there as no medical textbook that presented in a systematic way the development process of drugs [in the field.] The new book presents all the phases of development, from experimentation until the final approval by the authorities, while surveying the barriers and regulation,” said Mimoui. “The behavior of drugs in the body of a premie is different than that of adults, and there was a need to concentrate all accumulated knowledge in one volume and present it to professionals.”

One of the articles was written by Prof. Cathy Hammerman and colleagues on the use of paracetamol to close the ductus (blood vessels in the chest) in newborns as a substitute for open-heart surgery, while Mimouni write about the development

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