Chimeric antigen receptor with novel intracellular modules improves antitumor performance of T cells.

The excessive cytokine release and limited persistence represent major challenges for chimeric antigen receptor T (CAR-T) cell therapy in diverse tumors. Conventional CARs employ an intracellular domain (ICD) from the ζ subunit of CD3 as a signaling module, and it is largely unknown how alternative CD3 chains potentially contribute to CAR design. Here, we obtained a series of CAR-T cells against HER2 and mesothelin using a domain comprising a single immunoreceptor tyrosine-based activation motif from different CD3 subunits as the ICD of CARs.

Diversity of immune checkpoints in cancer immunotherapy.

Finding effective treatments for cancer remains a challenge. Recent studies have found that the mechanisms of tumor evasion are becoming increasingly diverse, including abnormal expression of immune checkpoint molecules on different immune cells, in particular T cells, natural killer cells, macrophages and others. In this review, we discuss the checkpoint molecules with enhanced expression on these lymphocytes and their consequences on immune effector functions.

VIM‑AS1 promotes proliferation and drives enzalutamide resistance in prostate cancer via IGF2BP2‑mediated HMGCS1 mRNA stabilization.

VIM‑AS1, a cancer‑specific long non‑coding RNA, has been recognized as a pivotal regulator in multiple types of cancer. However, the role of VIM‑AS1 in the proliferation and resistance to anti‑androgen therapy of LNCaP and C4‑2 prostate cancer cells remains to be determined. In the current study, gain‑and‑loss experiments were used to investigate the effects of VIM‑AS on the proliferation and anti‑androgen therapy of LNCaP and C4‑2 cells.

Antibody-drug conjugates targeting CD248 inhibits liver fibrosis through specific killing on myofibroblasts.

Background: Chronic liver injury induces pathological repair, resulting in fibrosis, during which hepatic stellate cells (HSCs) are activated and transform into myofibroblasts. CD248 is mainly expressed on myofibroblasts and was considered as a promising target to treat fibrosis. The primary aim of this study was to generate a CD248 specific antibody-drug conjugate (ADC) and evaluate its therapeutic efficacy for liver fibrosis and its safety in vivo.

Galectin-9 expression predicts poor prognosis in hepatitis B virus-associated hepatocellular carcinoma.

Objectives: The aim of this study was to explore the expression of Galectin-9 in hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC), evaluate its clinicopathological significance, and investigate whether Galecin-9 expression has prognostic value in HBV-associated HCC.

Methods: Immunohistochemistry staining was performed to examine the expression of Galectin-9 in paraffin-embedded tissues from 140 cases of HBV-associated HCC specimens. The association between Gal-9 expression, clinicopathological features and prognosis was analyzed by Kaplan-Meier method, log-rank test and Cox regression analysis.

Roles of HLA-G/KIR2DL4 in Breast Cancer Immune Microenvironment.

Human leukocyte antigen (HLA)-G is a nonclassical MHC Class I molecule, which was initially reported as a mediator of immune tolerance when expressed in extravillous trophoblast cells at the maternal-fetal interface. HLA-G is the only known ligand of killer cell immunoglobulin-like receptor 2DL4 (KIR2DL4), an atypical family molecule that is widely expressed on the surface of NK cells. Unlike other KIR receptors, KIR2DL4 contains both an arginine-tyrosine activation motif in its transmembrane region and an immunoreceptor tyrosine-based inhibitory motif (ITIM) in its cytoplasmic tail, suggesting that KIR2DL4 may function as an activating or inhibitory receptor.

The role of long non-coding RNAs in the pathogenesis of head and neck squamous cell carcinoma.

Head and neck cancers are a heterogeneous collection of malignancies of the upper aerodigestive tract, salivary glands, and thyroid. However, the molecular mechanisms underlying the carcinogenesis of head and neck squamous cell carcinomas (HNSCCs) remain poorly understood. Over the past decades, overwhelming evidence has demonstrated the regulatory roles of long non-coding RNAs (lncRNAs) in tumorigenesis, including HNSCC.

Antibody-drug conjugates targeting CD248 myofibroblasts effectively alleviate renal fibrosis in mice.

Myofibroblasts, or activated fibroblasts, play a critical role in the process of renal fibrosis. Targeting myofibroblasts to inhibit their activation or induce specific cell death has been considered to be an effective strategy to attenuate renal fibrosis. However, specific biomarkers for myofibroblasts are needed to ensure the efficacy of these strategies.

Interaction between HLA-G and NK cell receptor KIR2DL4 orchestrates HER2-positive breast cancer resistance to trastuzumab.

Despite the successful use of the humanized monoclonal antibody trastuzumab (Herceptin) in the clinical treatment of human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer, the frequently occurring drug resistance remains to be overcome. The regulatory mechanisms of trastuzumab-elicited immune response in the tumor microenvironment remain largely uncharacterized. Here, we found that the nonclassical histocompatibility antigen HLA-G desensitizes breast cancer cells to trastuzumab by binding to the natural killer (NK) cell receptor KIR2DL4.

Syngeneic homograft of framework regions enhances the affinity of the mouse anti-human epidermal receptor 2 single-chain antibody e23sFv.

e23sFv is a HER2-targeted single-chain variable fragment (scFV) that was characterized as the targeting portion of a HER2-targeted tumour proapoptotic molecule in our previous study. antibody affinity maturation is a method to enhance antibody affinity either by complementarity-determining region (CDR) mutagenesis or by framework region (FR) engraftment. In the present study, the affinity of e23sFv was enhanced using two strategies.

Ring finger protein 2 promotes colorectal cancer progression by suppressing early growth response 1.

Ring finger protein 2 (RNF2) is an important component of polycomb repressive complex 1. RNF2 is upregulated in many kinds of tumors, and elevated RNF2 expression is associated with a poor prognosis in certain cancers. To assess the function of RNF2 in colorectal cancer, we examined RNF2 protein levels in 313 paired colorectal cancer tissues and adjacent normal tissues.

The microRNA-424/503 cluster: A master regulator of tumorigenesis and tumor progression with paradoxical roles in cancer.

MicroRNAs (miRNAs) are a group of non-coding RNAs that play a crucial role in post-transcriptional gene regulation and act as indispensable mediators in several critical biological processes, including tumorigenesis, tissue homeostasis, and regeneration. MiR-424 and miR-503 are intragenic miRNAs that are clustered on human chromosome Xq26.3.

Interaction with CD68 and Regulation of GAS6 Expression by Endosialin in Fibroblasts Drives Recruitment and Polarization of Macrophages in Hepatocellular Carcinoma.

Fibroblasts and macrophages play key roles in the development of hepatocellular carcinoma (HCC). However, cross-talk between these two kinds of cells has not been well studied. Endosialin (CD248/TEM1) is a transmembrane glycoprotein that is expressed in certain cancer cells, tumor stromal cells, and pericytes.

A miR-205-LPCAT1 axis contributes to proliferation and progression in multiple cancers.

In the past two decades, miRNAs have been demonstrated to play critical roles in development and progression of malignant diseases. To identify the role and mechanism of miRNA are urgent for the application of miRNA-based therapeutics in cancers. MiR-205 is a conserved miRNA from the invertebrate to mammalian species.

Re-recognition of pseudogenes: From molecular to clinical applications.

Pseudogenes were initially regarded as "nonfunctional" genomic elements that did not have protein-coding abilities due to several endogenous inactivating mutations. Although pseudogenes are widely expressed in prokaryotes and eukaryotes, for decades, they have been largely ignored and classified as gene "junk" or "relics". With the widespread availability of high-throughput sequencing analysis, especially omics technologies, knowledge concerning pseudogenes has substantially increased.

Mir-494 inhibits osteoblast differentiation by regulating BMP signaling in simulated microgravity.

Although the BMPR-SMAD-RUNX2 signaling pathway plays widely recognized roles in BMP-induced osteogenesis, factors regulating this pathway remain to be defined. In this study, we used simulated microgravity models, which represent mechanical unloading conditions, to detect miRNAs that function in osteoblast differentiation. We found that miR-494 was persistently increased in C2C12 cells subjected to clinorotation conditions and in osteoblasts isolated from tail-suspended rats.

Expression of Prostate-Specific Membrane Antigen in Tumor-Associated Vasculature Predicts Poor Prognosis in Hepatocellular Carcinoma.

Introduction: Prostate-specific membrane antigen (PSMA) was originally found to be specifically expressed in normal prostate, and its expression was upregulated in almost all stages of prostate cancer. In recent years, PSMA was also found to be expressed in tumor-associated vasculature in many nonprostatic solid tumors. However, the expression pattern of PSMA in hepatocellular carcinoma (HCC) is not well studied.

A Novel Fully Human Antibody targeting Extracellular Domain of PSMA Inhibits Tumor Growth in Prostate Cancer.

Prostate cancer is the most commonly diagnosed malignancy in men and the second leading cause of cancer-related death. It is of vital importance to develop new strategies for prostate cancer therapy. PSMA (prostate-specific membrane antigen) is specifically expressed in prostate cancer and the neovasculature of certain cancer types, thus is considered to be an ideal target for cancer therapy.

UHRF1 promotes renal cell carcinoma progression through epigenetic regulation of TXNIP.

UHRF1 is an important epigenetic regulator that belongs to the UHRF family. Overexpression of UHRF1 has been found in many kinds of tumors and its overexpression is associated with poor prognosis and short survival in certain cancer types. However, its function in renal cell carcinoma (RCC) is not clear.

Therapeutic effects of human monoclonal PSMA antibody-mediated TRIM24 siRNA delivery in PSMA-positive castration-resistant prostate cancer.

: Prostate specific membrane antigen (PSMA) is specifically expressed on prostate epithelial cells and markedly overexpressed in almost all prostate cancers. TRIM24 is also up-regulated from localized prostate cancer to metastatic castration-resistant prostate cancer (CRPC). Because of the high relevance of TRIM24 for cancer development and the universal expression of PSMA in CPRC, we investigated the efficacy of human monoclonal PSMA antibody (PSMAb)-based platform for the targeted TRIM24 siRNA delivery and its therapeutic efficacy in CRPC and .

DNA methylation-regulated and tumor-suppressive roles of miR-487b in colorectal cancer via targeting MYC, SUZ12, and KRAS.

Human colorectal cancer (CRC), characterized by its high morbidity and lethality, seriously threatens human health and lives. MicroRNA-487b (miR-487b) is currently reported to be aberrantly expressed in several tumors, but the detailed functions and underlying mechanisms of miR-487b in CRC remain unclear. Here, we found that miR-487b is downregulated in CRC cell lines and is markedly decreased in tumor specimens derived from CRC patients.

Retraction Note: Nuclear factor of activated T cells 5 maintained by Hotair suppression of miR-568 upregulates S100 calcium binding protein A4 to promote breast cancer metastasis.

The authors are retracting this article [1] after an investigation by the Ethics Committee of the Fourth Military Medical University (Xi'an, Shaanxi, China) of the following concerns that had been raised with respect to two of the figures.

Construction of humanized anti-HER2 single-chain variable fragments (husFvs) and achievement of potent tumor suppression with the reconstituted husFv-Fdt-tBid immunoapoptotin.

As HER2 is frequently overexpressed in various malignancies, targeting HER2 is considered an efficient, highly selective antitumor therapy. HER2-targeted immunoconjugates are being developed and result in persistent remission of HER2-overexpressing tumors. However, many of the antibodies used as the targeting moiety are of murine origin and exhibit risk of inducing immunogenicity, limiting their antitumor therapeutic efficacy.