MicroRNAs (miRNAs) are small non-coding RNAs that typically inhibit the translation and stability of messenger RNAs (mRNAs). They are ~22 nucleotides long and control both physiological and pathological processes. Altered expression of miRNAs is often associated with human diseases. Thus, miRNAs have become important therapeutic targets, and some clinical trials investigating the effect of miRNA-based therapeutics in different types of diseases have already been conducted. The tumor microenvironment (TME) comprises cells such as infiltrated immune cells, cancer-associated endothelial cells (CAEs) and cancer-associated fibroblasts (CAFs), and all the components participate in the complicated crosstalk with tumor cells to affect tumor progression. Altered miRNAs expression in both these stromal and tumor cells could drive tumorigenesis. Thus, in this review, we discuss how aberrantly expressed miRNAs influence tumor progression; summarize the crosstalk between infiltrated immune cells, CAEs, CAFs, and tumor cells through miRNAs, and clarify the important roles of miRNAs in the tumor microenvironment, which may facilitate the clinical application of miRNA-based therapies.

Owing to the limited therapeutic efficacy of glioma vaccines, new strategies are required to improve cancer vaccines. Our study aimed to assess the therapeutic efficacy of a glioma vaccine called STDENVANT. This vaccine, comprising glioma stem‐like cell (GSC) lysate, dendritic cells (DCs), and Toll‐like receptor (TLR) 9 agonist CpG motif‐containing oligodeoxynucleotides (CpG ODNs), was assessed using a GL261‐C57BL/6 orthotopic mouse model of glioma. STDENVANT markedly improved survival and tumor regression by enhancing anti‐tumor immune function. Moreover, STDENVANT upregulated programmed death 1 (PD‐1) and its ligand PD‐L1 on effector T cells, DCs, and glioma tissues, resulting in the accumulation of regulatory T (Treg) cells in the brain and lymph nodes. Combinatorial administration of anti‐PD‐L1 antibody and STDENVANT conferred a greater survival advantage and decreased the Treg cell population in the brain. The present results indicate that PD‐L1 blockade can promote tumor regression via STDENVANT in a mouse model of glioma, and combinatorial administration of anti‐PD‐L1 antibody and STDENVANT increases the therapeutic anti‐tumor efficacy of treatment.

Cancer cell membranes (CCMs) are widely used as sources of tumor-associated antigens (TAAs) for the development of cancer vaccines. To improve the CCM-associated cancer vaccine efficiency, personalized cancer vaccines and effective delivery systems are required. In this study, we employed surgically harvested cancer tissues to prepare personalized CCMs for use as TAAs. Thioglycolic-acid-grafted poly(2-methyl-2-oxazoline)-block-poly(2-butyl-2-oxazoline-co-2-butenyl-2-oxazoline) (PMBEOx-COOH) was synthesized to load imiquimod (R837) efficiently. The personalized CCMs were then coated onto R837loaded PMBEOx-COOH nanoparticles (POxTA NPs/R837) to obtain surgically derived CCM-coated POxTA NPs (SCNPs/ R837). SCNPs/R837 efficiently travelled to the draining lymph nodes and were taken up and presented by plasmacytoid dendritic cells to elicit enhanced antitumor immune responses. When combined with programmed cell death-1 antibodies, SCNPs/R837 exhibited high efficiency corresponding to antitumor progression. Therefore, SCNP/R837 might represent a promising personalized cancer vaccine with significant potential for cancer immunotherapy.

Plasmacytoid dendritic cells (pDCs) express high levels of the toll-like receptors (TLRs) TLR7 and TLR9. In response to TLR7 and TLR9 ligands, pDCs are primary producers of type I interferons. Our previous study demonstrated that pDCs activated by the TLR7 ligand imiquimod (IMQ) and the TLR9 ligand CpG A can kill breast cancer cells in vitro and inhibit tumor growth in vivo. Moreover, we observed a distinctive morphological, phenotypic change in pDCs after activation by IMQ and CpG A. However, the effect of other TLR7 and TLR9 ligands on pDCs remains less understood. In this study, we treat pDCs with the TLR7 ligand IMQ, TLR7/8 ligands (CL097 and CL075), and three TLR9 ligands (different types of CpGs). The size of pDCs increased significantly after activation by TLR7, or TLR7/8 ligands. TLR7, TLR7/8, and TLR9 ligands similarly modulated cytokine release, as well as protein expression of pDC markers, costimulatory molecules, and cytotoxic molecules. Interestingly, TLR7/8 ligands, especially CL097, induced stronger responses. These results are relevant to the further study of the role and mechanism of pDC-induced antitumor effects and may aid in the development of a new strategy for future tumor immunotherapy.

Results: Among the 20 designed ODNs, HP06T07 significantly induced IFN-a, IL-6, and TNF-a secretion, and promoted B-cell activation and proliferation in a dose-dependent manner in human PBMCs and mouse splenocytes in vitro. Intratumoral injection of HP06T07 notably suppressed tumor growth and prolonged survival in the CT26 subcutaneous mouse model in a dose-dependent manner. HP06T07 administered nine times at 2-day intervals (I2) eradicated tumor growth at both primary and distant sites of CT26 tumors. HP06T07 restrained tumor growth by increasing the infiltration of T cells, NK cells, and plasmacytoid dendritic cells (pDCs). Conclusions: HP06T07, a novel CpG-C ODN, shows potent immunostimulatory activity in vitro and suppresses tumor growth in the CT26 subcutaneous mouse model.