Tumor-Associated Macrophages in Human Breast, Colorectal, Lung, Ovarian and Prostate Cancers

Abstract

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

COVID-19 and cytokine storm syndrome: can what we know about interleukin-6 in ovarian cancer be applied?

“…1). This is also observed in cancer [51]; in particular, in ovarian cancer, the study of tumor microenvironment in ascites offers the optimal condition to assess the relationship between the tumor and the immune system [52][53][54]. Indeed, the first study that demonstrated the peculiar metabolic changes of tumor microenvironment was carried out by Warburg in monocyte from peritoneal effusion induced by an abdominal implanted tumor (similarly to ovarian cancer) [55].…”

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“…Macrophages, an essential component of innate immunity, have high plasticity and can display divergent phenotypes and functions ( Lawrence and Natoli, 2011 ). In respond to different environmental stimuli, macrophages can develop into classically activated macrophages (M1 type) and alternatively activated macrophages (M2 type) ( Franklin and Li, 2016 ; Cassetta and Pollard, 2020 ; Larionova et al, 2020b ). M1 macrophages play a prominent role in immune surveillance by secreting pro-inflammatory cytokines and chemokines, and high antigen presentation.…”

NIR Bioluminescence Probe Enables Discovery of Diet-Induced Modulation of the Tumor Microenvironment via Nitric Oxide

“…Lastly, using BL660-NO in an orthotopic model of breast cancer we were able to study the impact of a high-fat diet on the TME. Although it has long been thought that a high-fat diet can promote tumor progression by creating an abnormal inflammatory TME, 71,72 the link to NO generation has been elusive owing to a dearth of real-time detection strategies of NO in vivo. Our data indicates that a high-fat diet can lead to greater macrophage infiltration of the TME, which in turn generates more NO via overexpression of iNOS.…”