Tailoring Nanomaterials for Targeting Tumor-Associated Macrophages.
Ovais Muhammad,Guo Mengyu,Chen Chunying
Advanced materials (Deerfield Beach, Fla.)
Advances in the field of nanotechnology together with an increase understanding of tumor immunology have paved the way for the development of more personalized cancer immuno-nanomedicines. Nanovehicles, due to their specific physicochemical properties, are emerging as key translational moieties in tackling tumor-promoting, M2-like tumor-associated macrophages (TAMs). Cancer immuno-nanomedicines target TAMs primarily by blocking M2-like TAM survival or affecting their signaling cascades, restricting macrophage recruitment to tumors and re-educating tumor-promoting M2-like TAMs to the tumoricidal, M1-like phenotype. Here, the TAM effector mechanisms and strategies for targeting TAMs are summarized, followed by a focus on the mechanistic considerations in the development of novel immuno-nanomedicines. Furthermore, imaging TAMs with nanoparticles so as to forecast a patient's clinical outcome, describing treatment options, and observing therapy responses is also discussed. At present, strategies that target TAMs are being investigated not only at the basic research level but also in early clinical trials. The significance of TAM-targeting biomaterials is highlighted, with the goal of facilitating future clinical translation.
Clinical relevance of tumour-associated macrophages.
Nature reviews. Clinical oncology
In the past decade, substantial advances have been made in understanding the biology of tumour-associated macrophages (TAMs), and their clinical relevance is emerging. A particular aspect that is becoming increasingly clear is that the interaction of TAMs with cancer cells and stromal cells in the tumour microenvironment enables and sustains most of the hallmarks of cancer. Therefore, manipulation of TAMs could enable improved disease control in a substantial fraction of patients across a large number of cancer types. In this Review, we examine the diversity of TAMs in various cancer indications and how this heterogeneity is being revisited with the advent of single-cell technologies, and then explore the current knowledge on the functional roles of different TAM states and the prognostic and predictive value of TAM-related signatures. We also review agents targeting TAMs that are currently being or will soon be tested in clinical trials, and how manipulations of TAMs can improve existing anticancer treatments. Finally, we discuss how TAM-targeting approaches could be further integrated into routine clinical practice, considering a precision oncology approach and viewing TAMs as a dynamic population that can evolve under treatment pressure.
Macrophage diversity in cancer revisited in the era of single-cell omics.
Trends in immunology
Tumor-associated macrophages (TAMs) have multiple potent functions in cancer and, thus, represent important therapeutic targets. These diverse functions highlight the heterogenous nature of TAMs. Recent single cell omics technologies have significantly advanced our understanding of the molecular diversity of TAMs. However, a unifying nomenclature of TAM diversity and annotation of their molecular signatures is lacking. Here, we review recent major studies of single cell transcriptome, epigenome, metabolome, and spatial omics of cancer with a specific focus on TAMs. We also propose a consensus model of TAM diversity and present avenues for future research.