Nano-immunotherapy for each stage of cancer cellular immunity: which, why, and what?

Abstract

Immunotherapy provides a new avenue for combating cancer. Current research in anticancer immunotherapy is primary based on T cell-mediated cellular immunity, which can be divided into seven steps and is named the cancer-immunity cycle. Unfortunately, clinical applications of cancer immunotherapies are restricted by inefficient drug delivery, low response rates, and unmanageable adverse reactions. In response to these challenges, the combination of nanotechnology and immunotherapy (nano-immunotherapy) has been extensively studied in recent years. Rational design of advanced nano-immunotherapies requires in-depth consideration of “which” immune step is targeted, “why” it needs to be further enhanced, and “what” nanotechnology can do for immunotherapy. However, the applications and effects of nanotechnology in the cancer-immunity cycle have not been well reviewed. Herein, we summarize the current developments in nano-immunotherapy for each stage of cancer cellular immunity, with special attention on the which, why and what. Furthermore, we summarize the advantages of nanotechnology for combination immunotherapy in two categories: enhanced efficacy and reduced toxicity. Finally, we discuss the challenges of nano-immunotherapy in detail and provide a perspective.

Hotspots and Frontiers in Inflammatory Tumor Microenvironment Research: A Scientometric and Visualization Analysis

“…Various NPs have been engineered individually to target various components in the TME, including CAFs and TAMs, owing to the role of the TME in tumor initiation, progression, metastasis, and therapeutic response ( Zhu et al, 2013 ; Miao and Huang, 2015 ; Ji et al, 2016 ) as well as to physiological conditions, such as acidic and hypoxic state ( Crayton and Tsourkas, 2011 ; Yang et al, 2019 ). In addition to targeting the TME, advanced NPs can be used to reinforce T-cell function, owing to their high effective cellular uptake, and controlled drug release ( Wang et al, 2021 ; Zuo et al, 2021 ). Despite challenges, such as safety and clinical translation, the application of nanotechnology represented by nanoparticles in tumor therapy is still very promising and worthy of further exploration by researchers.…”

Macrophage Reprogramming and Cancer Therapeutics: Role of iNOS-Derived NO

“…As stated earlier, induction of the innate immune response is initiated by activating the macrophage to M1-type, which produces NO/RNS, secrete TNF-α, IL-1β, and IL-6 with pro-inflammatory cytokines proteases such as MMP-9. Higher NO production activates downstream signaling pathways that perform a critical role in the cytotoxic activity of immune cells against tumor cells [12,114]. Furthermore, among other immune cells, NO synthesis in NK cells was shown to regulate their tumoricidal activity to some extent [115].…”

Supramolecular Nanostructures for Vaccines

“…Cancer immunity evolves in two steps: the preparatory and the effector ones [ 89 ]. The preparatory step takes place in the LN with release and presentation of cancer antigens for priming and activating T cells.…”

“…Therefore, nanotechnology is needed for surmounting these key biological barriers and effectively deliver chemo- and immune-therapeutic agents and vaccines to their sites of action; sensitive antigens easily degradable in the physiological medium can be protected using nanotechnologies able to increase their half-lives, minimize systemic toxicity, and promote their delivery to APCs in the LN [ 91 ]. Nanostructures such as NPs [ 5 , 17 , 43 , 92 ], bilayer fragments (BF) [ 4 , 12 ], or peptide supramolecular assemblies [ 93 ] become drained directly to the LNs, performing well in the preparatory step [ 89 ]. In the effector step, activated T cells should infiltrate the tumor, and stable, long-circulating, and targeted nanostructures could help T cells infiltration improving the outcomes of immunotherapies, which may give a low response rate due to the T-cell poor infiltration in the tumor tissue.…”

“…In a major, highly recommended review article, Irvine and coworkers considered that biotechnology combined with the nanomaterials science could bring about safer and more efficient vaccine formulations with major roles for the nanoparticles (NPs) [ 116 ]. In a fast moving field encompassing cancer nanotechnology [ 50 , 89 , 90 , 95 , 117 ], vaccinology against pathogenic viruses [ 61 , 62 , 96 , 97 , 98 , 99 , 100 , 106 , 118 ], and microbes such as bacteria [ 19 , 108 , 112 , 119 , 120 ], fungi [ 119 ], and parasites [ 22 , 120 , 121 , 122 , 123 , 124 ], elegant nanomaterials that are difficult to scale up for commercialization cannot become useful in clinics [ 116 , 125 ].…”