CD177 Deficiency Defines a Stable Subtype of Human Neutrophil Granulocytes with Tumor Promoting Activity.

The surface protein CD177 on human neutrophil granulocytes is linked to tissue infiltration. In most individuals, circulating neutrophils comprise distinct fractions of CD177-expressing (CD177+) and non-expressing (CD177-) cells, which differ functionally and influence disease outcomes. Currently, CD177 is considered a dynamic activation marker ultimately expressed by most neutrophils. Here, we show that, instead, CD177--neutrophils represent a stable subpopulation that never acquires CD177. CD177+- to CD177--neutrophil ratios persist over time in individuals, regardless of circadian rhythms or inflammation. Neutrophils remain CD177- during in vitro stimulation and are morphologically similar to CD177+-cells, but differ markedly regarding protein composition. Following stem cell transplantation, the host bone marrow defines the CD177-pattern of mature neutrophils. Functionally, CD177- neutrophils display pro-tumoral properties, including elevated arginase expression and enhanced tumor-supporting activity, are enriched in human head-and-neck cancer tissues, and associated with adverse clinical outcomes. Hence, CD177-expression or -absence defines stable human neutrophil subtypes with distinct functions.