Abstract
Solid tumors are initiated by genetic mutations in non-hematopoietic cells and progress into invasive malignant tumors. This tumor progression often culminates in metastatic disease that is largely refractory to current therapeutic modalities and thus dramatically reduces survival of tumor patients. As solid tumors account for more than 80% of cancer-related deaths, it is necessary to develop novel therapeutic strategies to treat the diseases. An attractive strategy is to target macrophages in both primary tumors [known as tumor-associated macrophages (TAMs)] and metastatic tumors [called metastasis-associated macrophages (MAMs)]. TAMs and MAMs are abundant in most solid tumors and can promote tumor metastasis. Several studies in various models of solid tumors suggest that the accumulation of TAMs, MAMs, and their progenitor cells is regulated by chemokine ligands released by tumor and stromal cells. Consequently, these macrophage-recruiting chemokines could be potential therapeutic targets to prevent malignant tumor development through disruption of the accumulation of pro-metastatic macrophages. This review will discuss the role of chemokine ligands and their receptors in TAM and MAM accumulation in primary and secondary tumor sites, and finally discuss the therapeutic potential of inhibitors against these macrophage-recruiting chemokines.
Highlights
Genetic alterations in non-hematopoietic cells can lead to uncontrolled cell proliferation that results in aberrant tissue mass called a solid tumor
Since loss of von Hippel-Lindau (VHL) is found in the majority of sporadic renal cell carcinoma (RCC) and JunB is up-regulated in the VHLdeficient RCC specimens [54, 55], these results suggest that CCL2 production by cancer cells via aberrant JunB expression might be a predominant mechanism to enhance tumor associated macrophage (TAM) accumulation in RCC
These results suggest that breast cancer cells can utilize CCL20-CCR6 and CCL5CCR5 signaling in order to recruit TAMs
Summary
Genetic alterations in non-hematopoietic cells can lead to uncontrolled cell proliferation that results in aberrant tissue mass called a solid tumor. It is widely recognized that both primary and metastatic tumors are composed of numerous stromal cells such as endothelial cells, pericytes, fibroblasts, mesenchymal stem cells, and a variety of immune cells [including regulatory T (Treg) cells, mast cells, neutrophils, myeloid-derived suppressor cells (MDSCs), and tumor associated macrophages (TAMs)] All of these stromal cells are known to promote tumor angiogenesis, cancer cell invasion, and/or disrupt immune surveillance, which helps progression of the metastatic cascade [5, 7]. Since activation of certain set of integrins progress each step of this cascade, blockade of the integrin-induced adhesion cascade has been suggested as a novel therapy for inflammatory diseases [15] Another key factor that regulates the directed migration and positioning of immune cells, including macrophages, are chemokines. I will discuss the therapeutic potential of TAM/MAM targeting by chemokine receptor antagonists, and consider the possibility of combining macrophage targeting with emerging immunotherapies for malignant tumors
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
