Monocytes are innate immune cells of the mononuclear phagocyte system that have emerged as important regulators of cancer development and progression. Our understanding of monocytes has advanced from viewing these cells as a homogenous population to a heterogeneous system of cells that display diverse responses to different stimuli. During cancer, different monocyte subsets perform functions that contribute to both pro- and antitumoral immunity, including phagocytosis, secretion of tumoricidal mediators, promotion of angiogenesis, remodeling of the extracellular matrix, recruitment of lymphocytes, and differentiation into tumor-associated macrophages and dendritic cells. The ability of cancer to evade immune recognition and clearance requires protumoral signals to outweigh ongoing attempts by the host immune system to prevent tumor growth. This review discusses current understanding of monocyte heterogeneity during homeostasis, highlights monocyte functions in cancer progression, and describes monocyte-targeted therapeutic strategies for cancer treatment.

Neutrophils patrol the bloodstream and tissues to kill microbes and guide subsequent innate and adaptive immune responses.

Monocytes are innate blood cells that maintain vascular homeostasis and are early responders to pathogens in acute infections. There are three well-characterized classes of monocytes: classical (CD14⁺CD16⁻in humans and Ly6C^hiin mice), intermediate (CD14⁺CD16⁺in humans and Ly6C⁺Treml4⁺in mice), and nonclassical (CD14⁻CD16⁺in humans and Ly6C^loin mice). Classical monocytes are critical for the initial inflammatory response. Classical monocytes can differentiate into macrophages in tissue and can contribute to chronic disease. Nonclassical monocytes have been widely viewed as anti-inflammatory, as they maintain vascular homeostasis. They are a first line of defense in recognition and clearance of pathogens. However, their roles in chronic disease are less clear. They have been shown to be protective as well as positively associated with disease burden. This review focuses on the state of the monocyte biology field and the functions of monocytes, particularly nonclassical monocytes, in health and disease.

Monocytes block tumor access to the lung: Metastatic cancer is especially hard to treat. In order to find potential new therapeutic targets, scientists are trying to understand the cellular events that promote or prevent metastasis. Hanna et al. now report a role for patrolling monocytes in blocking tumor metastasis to the lungs in mice. Tumors in mice engineered to lack patrolling monocytes showed increased metastasis to the lung but not to other tissues. Patrolling monocytes resided in the microvasculature of the lung, where they engulfed tumor material, which may explain how these cells prevent tumors from colonizing the lung. Science , this issue p. 985

Neutrophils are short-lived cells that play important roles in both health and disease. Neutrophils and monocytes originate from the granulocyte monocyte progenitor (GMP) in bone marrow; however, unipotent neutrophil progenitors are not well defined. Here, we use cytometry by time of flight (CyTOF) and single-cell RNA sequencing (scRNA-seq) methodologies to identify a committed unipotent early-stage neutrophil progenitor (NeP) in adult mouse bone marrow. Importantly, we found a similar unipotent NeP (hNeP) in human bone marrow. Both NeP and hNeP generate only neutrophils. NeP and hNeP both significantly increase tumor growth when transferred into murine cancer models, including a humanized mouse model. hNeP are present in the blood of treatment-naive melanoma patients but not of healthy subjects. hNeP can be readily identified by flow cytometry and could be used as a biomarker for early cancer discovery. Understanding the biology of hNeP should allow the development of new therapeutic targets for neutrophil-related diseases, including cancer.