Larionova Irina, Tuguzbaeva Gulnara, Ponomaryova Anastasia, Stakheyeva Marina, Cherdyntseva Nadezhda, Pavlov Valentin, Choinzonov Evgeniy, Kzhyshkowska Julia
Laboratory of Translational Cellular and Molecular Biomedicine, National Research Tomsk State University, Tomsk, Russia.
Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, Russia.
Front Oncol. 2020 Oct 22;10:566511. doi: 10.3389/fonc.2020.566511. eCollection 2020.
Tumor-associated macrophages (TAMs) are major innate immune cells that constitute up to 50% of the cell mass of human tumors. TAMs are highly heterogeneous cells that originate from resident tissue-specific macrophages and from newly recruited monocytes. TAMs' variability strongly depends on cancer type, stage, and intratumor heterogeneity. Majority of TAMs are programmed by tumor microenvironment to support primary tumor growth and metastatic spread. However, TAMs can also restrict tumor growth and metastasis. In this review, we summarized the knowledge about the role of TAMs in tumor growth, metastasis and in the response to cancer therapy in patients with five aggressive types of cancer: breast, colorectal, lung, ovarian, and prostate cancers that are frequently metastasize into distant organs resulting in high mortality of the patients. Two major TAM parameters are applied for the evaluation of TAM correlation with the cancer progression: total amount of TAMs and specific phenotype of TAMs identified by functional biomarkers. We summarized the data generated in the wide range of international patient cohorts on the correlation of TAMs with clinical and pathological parameters of tumor progression including lymphatic and hematogenous metastasis, recurrence, survival, therapy efficiency. We described currently available biomarkers for TAMs that can be measured in patients' samples (tumor tissue and blood). CD68 is the major biomarker for the quantification of total TAM amounts, while transmembrane receptors (stabilin-1, CD163, CD206, CD204, MARCO) and secreted chitinase-like proteins (YKL-39, YKL-40) are used as biomarkers for the functional TAM polarization. We also considered that specific role of TAMs in tumor progression can depend on the localization in the intratumoral compartments. We have made the conclusion for the role of TAMs in primary tumor growth, metastasis, and therapy sensitivity for breast, colorectal, lung, ovarian, and prostate cancers. In contrast to other cancer types, majority of clinical studies indicate that TAMs in colorectal cancer have protective role for the patient and interfere with primary tumor growth and metastasis. The accumulated data are essential for using TAMs as biomarkers and therapeutic targets to develop cancer-specific immunotherapy and to design efficient combinations of traditional therapy and new immunomodulatory approaches.
肿瘤相关巨噬细胞（TAM）是主要的先天性免疫细胞，在人类肿瘤的细胞组成中占比高达50%。TAM是高度异质性的细胞，起源于驻留组织特异性巨噬细胞和新招募的单核细胞。TAM的变异性很大程度上取决于癌症类型、阶段和肿瘤内异质性。大多数TAM由肿瘤微环境编程，以支持原发性肿瘤生长和转移扩散。然而，TAM也可以限制肿瘤生长和转移。在本综述中，我们总结了关于TAM在五种侵袭性癌症（乳腺癌、结直肠癌、肺癌、卵巢癌和前列腺癌）患者的肿瘤生长、转移及对癌症治疗反应中作用的相关知识，这些癌症常转移至远处器官，导致患者高死亡率。评估TAM与癌症进展相关性的两个主要TAM参数为：TAM的总量以及通过功能生物标志物鉴定的TAM的特定表型。我们总结了在广泛的国际患者队列中生成的数据，这些数据涉及TAM与肿瘤进展的临床和病理参数（包括淋巴和血行转移、复发、生存、治疗效果）的相关性。我们描述了目前可用于在患者样本（肿瘤组织和血液）中测量的TAM生物标志物。CD68是用于量化TAM总量的主要生物标志物，而跨膜受体（稳定素-1、CD163、CD206、CD204、MARCO）和分泌的几丁质酶样蛋白（YKL-39、YKL-40）用作功能性TAM极化的生物标志物。我们还认为，TAM在肿瘤进展中的特定作用可能取决于其在肿瘤内部分区的定位。我们得出了TAM在乳腺癌、结直肠癌、肺癌、卵巢癌和前列腺癌的原发性肿瘤生长、转移及治疗敏感性方面作用的结论。与其他癌症类型不同，大多数临床研究表明，结直肠癌中的TAM对患者具有保护作用，并干扰原发性肿瘤生长和转移。积累的数据对于将TAM用作生物标志物和治疗靶点以开发癌症特异性免疫疗法以及设计传统疗法与新免疫调节方法的有效组合至关重要。
