Macrophages are present in most human tissues and have very diverse functions. Activated macrophages are usually divided into two phenotypes, M1 macrophages and M2 macrophages, which are altered by various factors such as microorganisms, tissue microenvironment, and cytokine signals. Macrophage polarity is very important for infections, inflammatory diseases, and malignancies; its management can be key in the prevention and treatment of diseases. In this review, we assess the current state of knowledge on macrophage polarity and report on its prospects as a therapeutic target.

Chemokines, which are basic proteins that exert their effects via G protein-coupled receptors and a subset of the cytokine family, are mediators deeply involved in leukocyte migration during an inflammatory reaction. Chemokine (C-C motif) ligand 20 (CCL20), also known as macrophage inflammatory protein (MIP)-3α, liver activation regulated chemokine (LARC), and Exodus-1, is a small protein that is physiologically expressed in the liver, colon, and skin, is involved in tissue inflammation and homeostasis, and has a specific receptor C-C chemokine receptor 6 (CCR6). The CCL20-CCR6 axis has long been known to be involved in inflammatory and infectious diseases, such as rheumatoid arthritis and human immunodeficiency virus infections. Recently, however, reports have shown that the CCL20-CCR6 axis is associated with several cancers, including hepatocellular carcinoma, colorectal cancer, breast cancer, pancreatic cancer, cervical cancer, and kidney cancer. The CCL20-CCR6 axis promotes cancer progression directly by enhancing migration and proliferation of cancer cells and indirectly by remodeling the tumor microenvironment through immune cell control. The present article reviewed the role of the CCL20-CCR6 axis in cancer progression and its potential as a therapeutic target.

With 400,000 diagnosed and 180,000 deaths in 2020, renal cell carcinoma (RCC) accounts for 2.4% of all cancer diagnoses worldwide. The highest disease burden developed countries, primarily in Europe and North America. Incidence is projected to increase in the future as more countries shift to Western lifestyles. Risk factors for RCC include fixed factors such as gender, age, and hereditary diseases, as well as intervening factors such as smoking, obesity, hypertension, diabetes, diet and alcohol, and occupational exposure. Intervening factors in primary prevention, understanding of congenital risk factors and the establishment of early diagnostic tools are important for RCC. This review will discuss RCC epidemiology, risk factors, and biomarkers involved in reducing incidence and improving survival.

Chemokines are a small family of cytokines that were first discovered as chemotactic factors in leukocytes during inflammation, and reports on the relationship between chemokines and cancer progression have recently been increasing. The CCL2-CCR2 axis is one of the major chemokine signaling pathways, and has various functions in tumor progression, such as increasing tumor cell proliferation and invasiveness, and creating a tumor microenvironment through increased angiogenesis and recruitment of immunosuppressive cells. This review discusses the roles of the CCL2-CCR2 axis and the tumor microenvironment in cancer progression and their future roles in cancer therapy.

This study investigated tumor-associated macrophages activity in the microenvironment of renal cell carcinoma. Via a co-culture with macrophage-like cells differentiated from human monocyte cell line THP-1 and U937 cells, the migration ability of ACHN and Caki-1 cells, which are human renal cell carcinoma cell line cells, was significantly increased, as was the epithelial–mesenchymal transition change. A chemokine array identified the CCL20-CCR6 axis as a concentration-dependent signal in ACHN and Caki-1 cell migration. Akt in the ACHN and Caki-1 cells was activated by macrophage-like cells, and the CCL20 neutralizing antibody suppressed migration ability, epithelial–mesenchymal transition, and Akt phosphorylation in the ACHN and Caki-1 cells. Akt inhibitor AZD5363 also decreased the epithelial–mesenchymal transition change and migration ability in the ACHN and Caki-1 cells. In 42 renal cell carcinoma tissues, patients with CCR6 and macrophage infiltration indicated poor prognoses. In the tumor microenvironment of renal cell carcinoma, cancer cells are activated by CCL20 secreted by tumor-associated macrophages through Akt activation, followed by epithelial–mesenchymal transition and an acquired migration ability. Thus, inhibition of the CCL20-CCR6 axis may be a potential therapeutic strategy for renal cell carcinoma.

Several markers that reflect inflammation and nutritional status have been associated with oncological outcomes in many tumors. This study aimed to describe the impact of pretreatment inflammatory and nutritional indices on the oncological outcomes in nonmetastatic renal cell carcinoma (RCC). A total of 213 Japanese patients with nonmetastatic RCC at Kanazawa University Hospital between October 2007 and December 2018 were included. The inflammatory and nutritional indices, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), C-reactive protein-to-albumin ratio (CAR), prognostic nutritional index (PNI), and geriatric nutritional risk index (GNRI), were retrospectively analyzed. The optimal cutoffs for NLR, PLR, CAR, PNI, and GNRI were 2.18, 153.7, 0.025, 48.4, and 98, respectively. According to Kaplan–Meier curves, elevated NLR, PLR, CAR, and GNRI correlated with increased metastasis, while NLR and PNI correlated with worse overall survival (OS). In multivariate analysis, high CAR was an independent poor risk factor for metastasis (hazard ratio (HR), 3.08; 95% confidence interval (CI), 1.24–7.67; p = 0.016). Furthermore, high NLR showed an independent prognostic factor for worse OS (HR, 3.96; 95% CI, 1.01–15.59; p = 0.049). The pretreatment inflammatory and nutritional indices such as NLR and CAR might be promising prognostic factors for nonmetastatic RCC.