Dataset Information

Synergetic Functional Nanocomposites Enhance Immunotherapy in Solid Tumors by Remodeling the Immunoenvironment.

ABSTRACT: Checkpoint blockade immunotherapy has demonstrated significant clinical success in various malignant tumors. However, the therapeutic response is limited due to the immunosuppressive tumor microenvironment (ITM). In this study, a functional nanomaterial, layered double hydroxides (LDHs), carrying specific functional miR155 is developed to modulate ITM by synergistically repolarizing tumor associated macrophages (TAMs) to M1 subtype. LDH nanoparticles loaded with miR155 (LDH@155) exhibit superior ability in cellular uptake by murine macrophages, miR escape into the cytoplasm and TAMs specific delivery when introtumoral administration. Meanwhile, upon exposure to LDH@155, TAMs are significantly skewed to M1 subtype, which markedly inhibits myeloid-derived suppressor cells (MDSCs) formation and stimulates T-lymphocytes to secrete more interferon-γ (IFN-γ) cytokines in vitro. Introtumoral administration of LDH@155 reduces the percentage of TAMs and MDSCs in the tumor and elevates CD4+ and CD8+ T cell infiltration and activation, which can promote therapeutic efficiency of α-PD-1 antibody immunotherapy. Furthermore, it is found that LDH@155 significantly decreases the expression level of phosphorylated STAT3 and ERK1/2 and activates NF-κB expression in TAMs, indicating that the STAT3, ERK1/2, and NF-κB signaling pathways may involve in LDH@155-induced macrophage polarization. Overall, the results suggest that LDH@155 nanoparticles may, in the future, function as a promising agent for cancer combinational immunotherapy.

SUBMITTER: Yang L

PROVIDER: S-EPMC6469336 | biostudies-other | 2019 Apr

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

Synergetic Functional Nanocomposites Enhance Immunotherapy in Solid Tumors by Remodeling the Immunoenvironment.

Yang Linnan L Sun Jing J Liu Qiang Q Zhu Rongrong R Yang Qiannan Q Hua Jiahui J Zheng Longpo L Li Kun K Wang Shilong S Li Ang A

Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20190216 8

Checkpoint blockade immunotherapy has demonstrated significant clinical success in various malignant tumors. However, the therapeutic response is limited due to the immunosuppressive tumor microenvironment (ITM). In this study, a functional nanomaterial, layered double hydroxides (LDHs), carrying specific functional miR155 is developed to modulate ITM by synergistically repolarizing tumor associated macrophages (TAMs) to M1 subtype. LDH nanoparticles loaded with miR155 (LDH@155) exhibit superior ...[more]

PMID: 31016114

Similar Datasets

Project description:Definitive management of locoregionally advanced solid tumors presents a major challenge and often consists of a combination of surgical, radiotherapeutic and systemic therapy approaches. Upfront surgical treatment with or without adjuvant radiotherapy carries the risks of significant morbidities and potential complications that could be lasting. In addition, these patients continue to have a high risk of local or distant disease relapse despite the use of standard adjuvant therapy. Preoperative neoadjuvant systemic therapy has the potential to significantly improve clinical outcomes, particularly in this era of expanding immunotherapeutic agents that have transformed the care of patients with metastatic/unresectable malignancies. Tremendous progress has been made with neoadjuvant immunotherapy in the treatment of several locoregionally advanced resectable solid tumors leading to ongoing phase 3 trials and change in clinical practice. The promise of neoadjuvant immunotherapy has been supported by the high pathologic tumor response rates in early trials as well as the durability of these responses making cure a more achievable potential outcome compared with other forms of systemic therapy. Furthermore, neoadjuvant studies allow the assessment of radiologic and pathological responses and the access to biospecimens before and during systemic therapy. Pathological responses may guide future treatment decisions, and biospecimens allow the conduct of mechanistic and biomarker studies that may guide future drug development. On behalf of the National Cancer Institute Early Drug Development Neoadjuvant Immunotherapy Working Group, this article summarizes the current state of neoadjuvant immunotherapy of solid tumors focusing primarily on locoregionally advanced melanoma, gynecologic malignancies, gastrointestinal malignancies, non-small cell lung cancer and head and neck cancer including recent advances and our expert recommendations related to future neoadjuvant trial designs and associated clinical and translational research questions.

Dataset Information

Synergetic Functional Nanocomposites Enhance Immunotherapy in Solid Tumors by Remodeling the Immunoenvironment.

Publications

Synergetic Functional Nanocomposites Enhance Immunotherapy in Solid Tumors by Remodeling the Immunoenvironment.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets