Tumor-associated macrophages (TAMs) occupy an important position in the tumor microenvironment (TME), they are a highly plastic heterogeneous population with complex effects on tumorigenesis and development. TAMs secrete a variety of cytokines, chemokines, and proteases, which promote the remodeling of extracellular matrix, tumor cell growth and metastasis, tumor vessel and lymphangiogenesis, and immunosuppression. TAMs with different phenotypes have different effects on tumor proliferation and metastasis. TAMs act a pivotal part in occurrence and development of tumors, and are very attractive target to inhibit tumor growth and metastasis in tumor immunotherapy. This article reviews the interrelationship between TAMs and tumor microenvironment and its related applications in tumor therapy.
Neoantigen‐based immunotherapy is a promising treatment option for many types of cancer. However, its efficacy and abscopal effect are limited by impotent neoantigens, high treatment costs, and complications due to action of adjuvants. Here, the design and synthesis of nanovaccines are reported, based on self‐adjuvanted, polymer nanoparticles with in vivo neoantigen‐harvesting and molecular activating capabilities. These nanovaccines inhibit tumor growth significantly and prolong the survival of tumor‐bearing mice in both colon carcinoma 26 (CT26) and B16‐F10 tumor models. Mechanistic studies suggest that as‐synthesized nanovaccines can promote dendritic cell maturation and accumulation expeditiously in lymph nodes, leading to the expansion of cytotoxic CD8+ T cells. Moreover, these nanovaccines elicit abscopal effects in CT26 and B16‐F10 tumors without the need for adjuvants or immune checkpoint inhibitors. Combined with an anti‐PD‐L1 antibody, nanovaccines can evoke robust, long‐term memory immune response, as evidenced by tumor growth inhibition and high survival rates (∼ 67%) over 90 days. These results highlight the potential of using self‐adjuvanted nanovaccines as a simple, safe, and affordable strategy to boost neoantigen‐based cancer immunotherapy.
A challenge for bioprinting tissue constructs is enabling the viability and functionality of encapsulated cells. Rationally designed bioink that can create appropriate biophysical cues shows great promise for overcoming such challenges. Here, a nanoparticle-stabilized emulsion bioink for direct fabrication of porous tissue constructs by digital light processing based 3D bioprinting technology is introduced. The emulsion bioink is integrated by the mixture of aqueous dextran microdroplets and gelatin methacryloyl solution and is further rendered stable by 𝜷-lactoglobulin nanoparticles. After bioprinting, the printed tissue constructs create the macroporous structure via removal of dextran, thereby providing favorable biophysical cues to promote the viability, proliferation, and spreading of the encapsulated cells. Moreover, a trachea-shaped construct containing chondrocytes is bioprinted and implanted in vivo. The results demonstrate that the generated macroporous construct is of benefit to cartilage tissue rebuilding. This work offers an advanced bioink for the fabrication of living tissue constructs by activating the cell behaviors and functions in situ and can lead to the development of 3D bioprinting.
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