Cutting edges and therapeutic opportunities on tumor-associated macrophages in lung cancer

Abstract

Lung cancer is a disease with remarkable heterogeneity. A deep understanding of the tumor microenvironment (TME) offers potential therapeutic strategies against this malignant disease. More and more attention has been paid to the roles of macrophages in the TME. This article briefly summarizes the origin of macrophages, the mutual regulation between anti-tumoral immunity and pro-tumoral statuses derived from macrophage polarization, and the therapeutic opportunities targeting alternately activated macrophages (AAM)-type macrophage polarization. Among them, cellular components including T cells, as well as acellular components represented by IL-4 and IL-13 are key regulators driving the polarization of AAM macrophages. Novel treatments targeting macrophage-associated mechanisms are mainly divided into small molecule inhibitors, monoclonal antibodies, and other therapies to re-acclimate AMM macrophages. Finally, we paid special attention to an immunosuppressive subgroup of macrophages with T cell immunoglobulin and mucin domain-3 (TIM-3) expression. Based on cellular interactions with cancer cells, TIM3+ macrophages facilitate the proliferation and progression of cancer cells, yet this process exposes targets blocking the ligand-receptor recognition. To sum up, this is a systematic review on the mechanism of tumor-associated macrophages (TAM) polarization, therapeutic strategies and the biological functions of Tim-3 positive macrophages that aims to provide new insights into the pathogenesis and treatment of lung cancer.

Peripheral blood white blood cells, monocytes, basophils, aspartate aminotransferase, and prothrombin time ratio after two cycles of treatment were independently associated with efficacy of neoadjuvant chemoimmunotherapy in non-small cell lung cancer

“…A higher peripheral monocyte count has been reported as an independent predictor for poor 5-year disease-free survival in hepatocellular carcinoma (32). Intratumoral monocytes can convert to tumor-associated macrophages that contribute to the deactivation of cytotoxic T cells through secreting numerous immunosuppressive cytokines, such as IL-10, transforming growth factor-β, and nitric oxide (31,33). moMDSCs are a class of key immunosuppressive cells in the TME and hinder the activities of cytotoxic T cells, NK cells and antigenpresenting cells (20).…”

Exosomes: efficient macrophage-related immunomodulators in chronic lung diseases

“…In lung cancer, tumor-associated macrophages (TAMs) are closely associated with tumor development, invasion, and metastasis, influencing the tumor microenvironment, immune suppression, and angiogenesis ( Hu et al, 2022 ). TAMs are generally classified into two main subtypes: M1 macrophages and M2 macrophages.…”

Investigating Vitreous Cytokines in Choroidal Melanoma

“…When we compared vitreous cytokine levels between different primary tumor GEPdefined prognostic classes (high-risk Class 2 vs. low-risk Class 1) in our CM group, we identified six differentially expressed cytokines (MCP-3/CCL7, PDGF-AB/BB, TNF-β, G-CSF, IL-13, and IL-3) (Figure S2). In previous cancer studies [26,46,[60][61][62][63][64], these cytokines have been individually linked to the regulation of tumor growth, survival, angiogenesis, and/or escape from the immune response. In the PCA plot generated using the vitreous expression profiles of these six cytokines, all but one (10 of 11) Class 1 samples clustered together and separately from the Class 2 samples (Figure 2).…”