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

Cancer statistics show that recent improvements in cancer management are only mildly effective in the absence of reliable biomarkers for the detection, diagnosis and monitoring of malignant disease. Recently circulating nucleic acids have been suggested as potential biomarker candidates to fill this role. Areas covered: This review focuses on the different types of circulating RNA biomarkers under investigation, describing the latest advances in their development and application to clinical settings, as well as challenges that researchers face in the process. Immediate perspectives of the field are outlined, and authors' recommendations on the best progression path are provided. Expert commentary: The development of RNA-based cancer biomarkers is a thriving area of biomedical research that has progressed significantly over the last decade. However, it seems that it is now at the point, where unless several key issues are resolved, no significant progress can be made further. Currently several areas of biomarker research require re-assessment, as indicated by the latest findings regarding the biology of circulating nucleic acids and the accumulated data of their analysis using various techniques. Additionally, regulating agencies need to be working alongside researchers to facilitate faster and easier adoption of new effective biomarkers into the clinical practice.

Recent studies provide evidence of the circulating nucleome organization complexity indicating that discovery of extracellular DNA generation and circulation patterns in healthy condition and cancer is essential to enable the development of proper approaches for the selection of valid diagnostic markers.

No abstract