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

Abstract

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.

Development of an immune-related gene pairs signature for predicting clinical outcome in lung adenocarcinoma

“…Macrophages M0 may polarized into different types: M1 and M2 [20,21]. Several studies have revealed that macrophages M1 could promote LUAD cells proliferation, invasion and metastasis [22][23][24] and an increased density of macrophages M1 in TME was associated with poor prognosis in LUAD [25,26], which was in accord with the nding in this study. Previous researches demonstrated accumulating memory B cells were strongly correlated with favorable clinical outcomes in various tumors [27].…”

Current perspectives on the immunosuppressive tumor microenvironment in hepatocellular carcinoma: challenges and opportunities

“…These cells are now known as MDSCs, a heterogeneous population of immature myeloid cell. MDSCs are also plastic and respond to microenvironment signals [40][41][42]. MDSCs can differentiate into macrophages, granulocytes and dendritic cells (DCs) in vitro.…”

“…It has been reported that the immunosuppressive activity of MDSCs in the tumor microenvironment mainly includes (a) inducing differentiation and expansion of Tregs; (b) inhibiting the polarization of DCs, NKs and macrophages to the M2 phenotype; (c) depriving T cells of essential amino acids; (d) inducing oxidative stress ( Fig. 2) [40][41][42][43]. We mainly reviewed the MDSCs in the tumor growth, angiogenesis, and metastasis of HCC in this context (Table 1) and an increase in immunosuppressive cytokine levels in HCC patients, revealing the potential mechanistic network for immune disorders in HCC patients compared with the normal control group [55].…”

CD2+ T-helper 17-like cells differentiated from a CD133+ subpopulation of non-small cell lung carcinoma cells promote the growth of lung carcinoma

“…The size of each subcutaneously transplanted tumor was measured with the Vevo 2100 Imaging Platform (Visual Sonics, Canada). The tumor volume was calculated with the following formula: tumor volume = 0.5 × long diameter × short diameter 2 .…”

“…Non-small cell lung carcinoma (NSCLC) is the most commonly diagnosed cancer and the leading cause of cancerassociated death (1). The prognosis of NSCLC is poor, and the survival rate is only 15% after 5 years because many of these patients ultimately do not respond to chemoradiotherapy, which is associated with unimaginable degree of cellular heterogeneity within a single tumor (2). The heterogeneity of tumor may correlates with cancer stem cells (CSCs) or tumor-initiating cells (TICs) which may be responsible for NSCLC treatment failure which includes local recurrence, distant metastasis, and the limitations of therapeutic agents (3).…”