Macrophage Origin, Metabolic Reprogramming and IL-1 Signaling: Promises and Pitfalls in Lung Cancer

Description

Macrophages are tissue-resident cells that act as immune sentinels to maintain tissue integrity, preserve self-tolerance and protect against invading pathogens. Lung macrophages within the distal airways face around 8000–9000 L of air every day and for that reason are continuously exposed to a variety of inhaled particles, allergens or airborne microbes. Chronic exposure to irritant particles can prime macrophages to mediate a smoldering inflammatory response creating a mutagenic environment and favoring cancer initiation. Tumor-associated macrophages (TAMs) represent the majority of the tumor stroma and maintain intricate interactions with malignant cells within the tumor microenvironment (TME) largely influencing the outcome of cancer growth and metastasis. A number of macrophage-centered approaches have been investigated as potential cancer therapy and include strategies to limit their infiltration or exploit their antitumor effector functions. Recently, strategies aimed at targeting IL-1 signaling pathway using a blocking antibody have unexpectedly shown great promise on incident lung cancer. Here, we review the current understanding of the bridge between TAM metabolism, IL-1 signaling, and effector functions in lung adenocarcinoma and address the challenges to successfully incorporating these pathways into current anticancer regimens.

Abstract

International audience

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