Neutrophil depletion’s effect on lung cancer – UROP Spring Symposium 2021

Neutrophil depletion’s effect on lung cancer

Jason Manassa


Research Mentor(s): Stefanie Galban, Assistant Professor
Research Mentor School/College/Department: Radiology, Michigan Medicine
Presentation Date: Thursday, April 22, 2021
Session: Session 5 (3pm-3:50pm)
Breakout Room: Room 17
Presenter: 1

Event Link


Lung cancer remains the leading cause of cancer-related deaths worldwide, with non-small cell lung cancer (NSCLC) making up 85% of lung cancers. NSCLC is comprised of adenocarcinomas and lung squamous cell carcinoma and develops primarily in individuals over the age of 55 who regularly smoke. Current research on the tumor microenvironment revealed that neutrophils, a type of white blood cell responsible for fighting infections, actually aids tumor progression by allowing the creation of chemotaxis that promote tumor metastasis. Additionally, current immunotherapies are only 30% effective. This study looks specifically at how neutrophils affect the tumor microenvironment (TME). We hypothesized that if neutrophils depleted in mice with adenocarcinoma they would decrease in tumor burden, as the chemotaxis transport mechanism for cancer cells would be gone. We have established a murine model of lung cancer, wherein expression of oncogenic Kras and p53 can be controlled genetically, allowing activation of oncogenic Kras to initiate tumor growth, tumor eradication upon Kras depletion and re-activation as a means to model relapse, and p53 speeds up tumor progression. Control mice were used alongside our cancer inducible mice, to test the effects of neutrophil depletion. Half of the mice were given the antibody IgG that has no effect on neutrophil depletion while GR-1, a neutrophil depleted antibody was given to the other half. After 4-week treatment, we took lung tissue; paraffin embedded it and stained it with HE. Tumors were counted and the subsequent analysis revealed 1) Mice with both Kras and p53 on have more tumors than those with just Kras on 2) Neutrophil depletion resulted in lower tumor counts for mice. In summary, neutrophils play likely a tumor-promoting role in lung cancer. Depletion of neutrophils by antibodies resulted in a decrease in tumor burden suggesting new treatment option for lung cancer patients by modulating TME.

Authors: Jason Manassa
Research Method: Laboratory Research

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