For the first time in a human tumor, scientists from the Perelman School of Medicine at the University of Pennsylvania have discovered a “hybrid lymphocyte” - part neutrophil and part antigen-presenting cell. Will learning more about this immune cell lead to a new generation of cancer immunotherapy drugs?
In their study published in Cancer Cell
, Pennsylvania scientists aimed to characterize the so-called tumor-associated neutrophil (TAN) that was found at high levels in the microenvironment of tumors in samples of early-stage lung cancer. Neutrophils are normally first-responders to an infection site, killing pathogens by engulfing them and releasing perforating enzymes. Antigen-presenting cells include a variety of different lymphocytes that intercept pathogens and display pieces of them on their cell surface for cells like T lymphocytes to recognize, warning them of an invasion.
During their research, the scientists wanted to know how TANs helped reduce tumor volume. In order to potentially manipulate TAN activity for future immunotherapies, they would need to understand TAN function first. The researchers investigated closely how TAN activity affected the response of cytotoxic T cells, another immune cell type that aggressively targets tumors.
“Our findings demonstrate that the early-stage lung tumor microenvironment can drive neutrophils to differentiate into a cell subset with enhanced anti-tumor capabilities,” explained coauthor of the study Sunil Singhal, MD. “Interestingly, this hybrid population disappears as tumors enlarge.”
In addition to targeting and fighting cancer cells, cytotoxic T cells kill viruses, bacteria, and even protozoa. Cytotoxic T cells cleverly cause death in foreign cells by reprogramming their cellular machinery so they will undergo apoptosis, a process of programmed cell death.
“Perhaps if we can expand the hybrid neutrophils in patients early on, we can augment anti-tumor T cell activity,” suggested senior author of the study Evgeniy B. Eruslanov, PhD. Considering the role of cytotoxic T cells in other pathologies in addition to cancer, therapy using hybrid neutrophils could be useful for multiple diseases in the future.
Sources: University of Pennsylvania School of Medicine
, Immunobiology: The Immune System in Health and Disease. 5th edition.
, PubMed Health