Therapeutic strategies of manipulating tumor-related neutrophils as new exciting players in cancer immunotherapy

Prof. Zvi Fridlender, Head, Department of Internal Medicine D, Head, Laboratory of Lung Cancer Research and Head, Hadassah Center for COPD and Smoking Related Damages

The debatable strategy of making use of the immune system to treat cancer dates back decades and relies on the ability of the immune system to be able to eliminate malignant cells. T cells are part of the immune system and are a type of white blood cell that circulates around our bodies, scanning for cellular abnormalities, infections and may help fight cancer. In the last few years, promising drugs were developed implementing this strategy of inducing T -cells to attack tumors. Unfortunately, only a small number of patients benefited from these drugs. Prof. Fridlender has been focusing on neutrophils since they are the most abundant type of white blood cells and form an essential part of the innate immune system. They are also considered the first line of immune defense. Due to the complexity of studying these cells, their function, especially in tumor development, has not been extensively investigated. After many years of controversies on the role neutrophils play in cancer, Prof. Fridlender and his research team were the first to describe the unexpected findings that neutrophils possess a dual role of either promoting or inhibiting cancer formation and development. This “switch” can be characterized as a double-edged sword. After describing this important finding in the tumor itself, he also recently characterized different types of circulating neutrophils in cancer.

Clinical observations and laboratory studies have reported that the presence of neutrophils in tumors is associated with poor prognosis for the patient. Since neutrophils are indispensable in combating infection and facilitators of wound healing and they are now being recognized as playing an important and active role in the progression of cancer, Prof. Fridlender is focusing on evaluating the mechanism(s) regulating different tumor-related neutrophil sub-populations and the interplay between them. He is looking into unveiling how they affect tumor cells, and how they can influence the immune system, in addition to how tumor cells affect the types and numbers of neutrophils. Their dual role of either supporting tumor or anti-tumor development depending on their characteristics of maturity, localization and immune suppression is an important investigative goal that will influence tumor growth and the development of metastases directly or in combination with other conventional treatments. Thus, Prof. Fridlender plans to 1) identify the characteristics of the different subpopulations of neutrophils and the interplay between them (since some groups may have anti-tumor capabilities in human cancer while others may not); 2) unveil how neutrophils affect tumor growth and development and how they influence the immune system; 3) manipulate selected types of neutrophils in order to switch those neutrophils that support tumor growth into those that fight cancer as well as develop strategies to direct the immune system against the tumor. In order words, Prof. Fridlender plans to re-educate subpopulations of neutrophils to our benefit. He will be using mouse models of thoracic malignancies, lung and breast cancer, and study also samples from human blood and tissue.

In this investigation, Prof. Fridlender aims to use neutrophils for diagnosis, prognosis, follow-up and eventually develop strategies to direct the immune system as a whole, and specifically the neutrophils against the tumor and provide new therapeutic options for cancer patients.