RT Journal Article
SR Electronic
T1 Human G-MDSCs are neutrophils at distinct maturation stages promoting tumor growth in breast cancer
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202000893
DO 10.26508/lsa.202000893
VO 3
IS 11
A1 Meliha Mehmeti-Ajradini
A1 Caroline Bergenfelz
A1 Anna-Maria Larsson
A1 Robert Carlsson
A1 Kristian Riesbeck
A1 Jonas Ahl
A1 Helena Janols
A1 Marlene Wullt
A1 Anders Bredberg
A1 Eva Källberg
A1 Frida Björk Gunnarsdottir
A1 Camilla Rydberg Millrud
A1 Lisa Rydén
A1 Gesine Paul
A1 Niklas Loman
A1 Jörgen Adolfsson
A1 Ana Carneiro
A1 Karin Jirström
A1 Fredrika Killander
A1 Daniel Bexell
A1 Karin Leandersson
YR 2020
UL https://www.life-science-alliance.org/content/3/11/e202000893.abstract
AB Myeloid-derived suppressor cells (MDSCs) are known to contribute to immune evasion in cancer. However, the function of the human granulocytic (G)-MDSC subset during tumor progression is largely unknown, and there are no established markers for their identification in human tumor specimens. Using gene expression profiling, mass cytometry, and tumor microarrays, we here demonstrate that human G-MDSCs occur as neutrophils at distinct maturation stages, with a disease-specific profile. G-MDSCs derived from patients with metastatic breast cancer and malignant melanoma display a unique immature neutrophil profile, that is more similar to healthy donor neutrophils than to G-MDSCs from sepsis patients. Finally, we show that primary G-MDSCs from metastatic breast cancer patients co-transplanted with breast cancer cells, promote tumor growth, and affect vessel formation, leading to myeloid immune cell exclusion. Our findings reveal a role for human G-MDSC in tumor progression and have clinical implications also for targeted immunotherapy.