Researchers at the Institute of oncology research (IOR, affiliated to USI and member of Bios+), in collaboration with researchers from the University of Padova, have made a groundbreaking discovery that could change the way we think about aging and immune cells offering a potential new target for treatments in cases of prostate cancer.
The study is published in the prestigious journal Cancer Cell.
Neutrophils represent 50–70% of the myeloid-derived white circulating cells in human blood and are mainly involved in the human innate immunity against invading pathogens.
Following specific tumor-produced substances, cancer cells can recruit immunosuppressive neutrophils, a subset of immune cells driving immune suppression, tumor proliferation, and treatment resistance.
In advanced prostate cancers, expansion of circulating neutrophils correlates with worse overall survival and decreased sensitivity to standard therapies, such as anti-androgens and chemotherapy. Such findings have paved the way to explore new therapies aimed at blocking the tumor recruitment of these cells.
Researchers at the IOR and University of Padova have now identified a new mechanism of therapy resistance that involves neutrophils.
Physiologically, neutrophils are known to have a short half-life. Researchers directed by Prof. Andrea Alimonti, MD, and Prof. Arianna Calcinotto, PhD at the IOR identified a subset of neutrophils that persists in the tumor microenvironment and are more immunosuppressive tumor-promoting than canonical immunosuppressive neutrophils. These aged neutrophils are able to ignite tumor development and induce therapy resistance.
These results reveal an alternative mechanism of tumor immune evasion and support the development of new anticancer therapies based on immune-senolytics that target senescent-like neutrophils.
“Our results represent a significant finding, shedding light on how cancer cells interact with the immune system at the molecular level,” said Nicolò Bancaro, first author of the publication.
“By targeting specific mechanisms of aging in the immune system with immune-senolytics, it may be possible to prevent or delay age-related diseases such as Alzheimer’s, Parkinson’s, and cancer.” Anticipated Prof. Alimonti.
Link to the publication: https://authors.elsevier.com/c/1ggtU5TA51da46
This work was supported by the Prostate Cancer Foundation 2019 SPGFZE-PCF Challenge Award to Dr. Alimonti and the 2019 Merck & AstraZeneca-PCF Young Investigator Award to Arianna Calcinotto, PhD.