A groundbreaking research endeavor led by the A*STAR.Singapore Immunology Network (A*STAR.SIgN) has uncovered a profound shift in the behavior of neutrophils, a vital component of the body's immune system, within certain cancer contexts. Rather than combating malignancies, these neutrophils undergo a transformation that actively fosters tumor growth.
Through meticulous examination of neutrophils as they infiltrate tumors, scientists at A*STAR.SIgN have discerned distinct markers distinguishing tumor-promoting neutrophils from their ordinary counterparts found elsewhere in the body. Neutrophils typically act as frontline defenders against infections, making their depletion during chemotherapy a risky proposition for cancer patients, who become vulnerable to life-threatening infections.
The ability to pinpoint tumor-promoting neutrophils marks a pivotal advancement, offering a novel strategy to target tumors while safeguarding essential immune responses. The study, “Deterministic reprogramming of neutrophils in tumors,” was published in Science on 12 January 2024.
Neutrophils, recognized as the immune system's rapid responders, swiftly migrate from the bloodstream to tissues to combat pathogens. In cancer settings, diverse neutrophil populations within tumors have been implicated in fueling tumor progression, leading to poorer clinical outcomes. However, the mechanisms driving the generation and cooperative actions of these distinct neutrophil types remained elusive, impeding precise targeting of tumor-promoting neutrophils.
Employing an experimental model of pancreatic cancer, A*STAR.SIgN researchers unveiled a phenomenon termed “reprogramming,” wherein neutrophils assume altered characteristics and functions upon infiltrating tumors, consolidating into a unified population irrespective of their origins. By elucidating the reprogramming process, the team gained insights into how these neutrophils sustain tumor growth.
Reprogrammed neutrophils facilitate the formation of new blood vessels within tumor cores, enabling tumors to overcome oxygen and nutrient limitations. By selectively blocking this vessel-promoting activity or disrupting neutrophil-tumor interactions, researchers successfully curtailed pancreatic tumor growth in preclinical models.
Moreover, analysis of human datasets revealed similar instances of neutrophil reprogramming in various solid cancers, suggesting a conserved pathway whereby neutrophils promote tumor growth. This study paves the way for innovative therapeutic strategies targeting neutrophil reprogramming, complementing existing treatments and immunotherapies aimed at bolstering the immune system's ability to eradicate tumors.
Source: Agency for Science, Technology and Research (A*STAR), Singapore