Department of Biochemistry, ICBS/UFRGS, and National Institutes for Science and Technology - Translational Medicine (INCT-TM), Porto Alegre (RS), Brazil.
Histol Histopathol. 2014 Jan;29(1):21-31. doi: 10.14670/HH-29.21. Epub 2013 Aug 13.
Lung cancer is the leading cause of cancer-related deaths worldwide. Non-small cell lung cancer (NSCLC) accounts for 80% of all lung malignancies. Tumor-associated macrophages (TAM) are abundant components of NSCLC. Although under certain conditions TAM can kill tumor cells, they can also act as tumor promoters secreting a variety of factors that directly stimulate tumor invasion and metastasis. TAM presents two distinct phenotypes: the classically activated (or M1) phenotype, which is highly pro-inflammatory (phagocytic and cytotoxic), and the alternatively activated (or M2) phenotype, which has anti-inflammatory and pro-tumoral properties. The polarization status of TAM depends on stimulating factors from the tumor microenvironment, and some in vitro evidence implies that the phagocytosis of apoptotic bodies derived from tumoral cells is a key factor in M1/M2 modulation, raising the question of whether the evaluation of the apoptotic index (AI) and macrophage polarization have a prognostic role in NSCLC patient survival. The present article systematically reviewed the published series of clinical data that correlated the AI and/or macrophage densities and polarization status (M1/M2) with the outcome of non-small cell lung cancer patients. Even though an overwhelming body of clinical data support that TAM's density, micro-anatomical localization, phenotype and intra-tumoral AI are independent predictors of survival time, no study to date has been conducted to evaluate the impact of these parameters altogether in NSCLC patient outcome. Joint analysis of these biologic factors in future studies might reveal their prognostic value in the management of NSCLC cases.
肺癌是全球癌症相关死亡的主要原因。非小细胞肺癌（NSCLC）占所有肺癌恶性肿瘤的 80%。肿瘤相关巨噬细胞（TAM）是 NSCLC 的丰富组成部分。尽管在某些条件下 TAM 可以杀死肿瘤细胞，但它们也可以作为肿瘤促进剂分泌各种直接刺激肿瘤侵袭和转移的因子。TAM 呈现出两种截然不同的表型：经典激活（或 M1）表型，具有高度促炎（吞噬和细胞毒性）特性，以及交替激活（或 M2）表型，具有抗炎和促肿瘤特性。TAM 的极化状态取决于肿瘤微环境中的刺激因子，一些体外证据表明，吞噬来自肿瘤细胞的凋亡小体是 M1/M2 调节的关键因素，这引发了一个问题，即评估凋亡指数（AI）和巨噬细胞极化是否对 NSCLC 患者的生存预后具有作用。本文系统地综述了已发表的临床数据系列，这些数据将 AI 和/或巨噬细胞密度和极化状态（M1/M2）与非小细胞肺癌患者的结局相关联。尽管大量的临床数据支持 TAM 的密度、微解剖定位、表型和肿瘤内 AI 是生存时间的独立预测因子，但迄今为止尚无研究评估这些参数在 NSCLC 患者结局中的综合影响。在未来的研究中联合分析这些生物学因素可能会揭示它们在 NSCLC 病例管理中的预后价值。
