Immunosuppressive reprogramming of neutrophils by lung mesenchymal cells promotes breast cancer metastasis.
Document Type
Article
Publication Date
2-24-2023
Original Citation
Gong Z,
Li Q,
Shi J,
Li P,
Hua L,
Shultz LD,
Ren G.
Immunosuppressive reprogramming of neutrophils by lung mesenchymal cells promotes breast cancer metastasis. Sci Immunol. 2023;8(80):eadd5204.
Keywords
JMG, SS1, Animals, Mice, Neutrophils, Cyclooxygenase 2, Lung, Lung Neoplasms, Killer Cells, Natural
JAX Source
Sci Immunol. 2023;8(80):eadd5204.
ISSN
2470-9468
PMID
36800412
DOI
https://doi.org/10.1126/sciimmunol.add5204
Grant
This work was supported by grants from the NIH (R00- CA188093, R37-CA237307, R01-CA251433, and P30-CA034196 to G.R. and R24-OD026440 to L.D.S.). Q.L. is supported by the Pyewacket Fund at the Jackson Laboratory. Z.G. is supported by the Brooks Scholar Award Program at the Jackson Laboratory.
Abstract
Neutrophils, the most abundant innate immune cells, function as crucial regulators of the adaptive immune system in diverse pathological conditions, including metastatic cancer. However, it remains largely unknown whether their immunomodulatory functions are intrinsic or acquired within the pathological tissue environment. Here, using mouse models of metastatic breast cancer in the lungs, we show that, although neutrophils isolated from bone marrow (BM) or blood are minimally immunosuppressive, lung-infiltrating neutrophils are robustly suppressive of both T cells and natural killer (NK) cells. We found that this tissue-specific immunosuppressive capacity of neutrophils exists in the steady state and is reinforced by tumor-associated inflammation. Acquisition of potent immunosuppression activity by lung-infiltrating neutrophils was endowed by the lung-resident stroma, specifically CD140a