Copper is an essential microelement for the body and a necessary coregulator for enzymatic reactions, yet an unbalanced copper level promotes reactive oxidation and cytotoxicity, which ultimately induces cell death. Several small molecules targeting copper-induced cell death have been investigated, yet few showed promising therapeutic effects in clinical trials. In March 2022, Science first introduced the concept and mechanisms of cuproptosis, suggesting that copper-induced cell death targets the tricarboxylic acid (TCA) cycle via protein lipoylation. Does this novel form of cell death take part in tumorigenesis or tumor progression? Is cuproptosis related to clinical outcomes of diseases? Is there a cuproptosis-related panel for clinical practice in cancer treatment? Herein, based on 942 samples of lung adenocarcinoma (LUAD), we analyzed on gene set level the existence and predictive value of cuproptosis in disease diagnosis and treatment. We screened out and identified the “cupLA” panel which indicates the risk of LUAD occurrence, clinicopathological features of LUAD patients, and could guide clinicians to refine LUAD subtypes and make treatment choices.
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.
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