Prognostic biomarker CPEB3 and its associations with immune infiltration in clear cell renal cell carcinoma.

The role and underlying mechanism of cytoplasmic polyadenylation element binding protein 3 (CPEB3) in clear cell renal cell carcinoma [ccRCC progression remain poorly characterized. The present study was designed to evaluate the role of CPEB3 in ccRCC and its clinical associations. The overall response rate of first-line therapies (ICIs combined with VEGFR-TKIs or ICI combination) for ccRCC] is 42.0-59.3%, so a number of patients with ccRCC do not benefit from these therapies. To avoid immunosurveillance and immune killing, tumor cells decrease immunogenicity and recruit immunosuppressive cells such as regulatory T cells (Tregs). Tregs inhibit the development of anti-tumor immunity, thereby hindering immune surveillance of cancer and preventing effective anti-tumor immune response in tumor-bearing hosts. The present study analyzed clinical specimens from patients ccRCC and then examined the role of CPEB3 in ccRCC via bioinformatics analysis. CPEB3 expression was significantly reduced in ccRCC compared with normal tissue and low CPEB3 expression was associated with poor overall survival. Moreover, CPEB3 expression was an independent predictor of survival. CPEB3 expression was positively associated with immune biomarkers [CD274, programmed cell death 1 ligand 2, Hepatitis a virus cellular receptor 2, Chemokine (C-X-C motif) ligand (CXCL)9, CXCL10, Inducible T cell costimulatory, CD40, CD80 and CD38] that improve the outcome of anti-tumor immune responses. CPEB3 expression in ccRCC also affected the status of 24 types of infiltrating immune cell, of which Tregs were the most significantly negatively correlated cell type. CPEB3 may serve as a prognostic biomarker in ccRCC and its mechanism may be related to the regulation of Tregs.

In Vivo and In Vitro Assay to Address Dendritic Cell Antigen Cross-Presenting Capacity.

Antigen cross-presentation by dendritic cells is an important pathway to prime CD8+ T cells in infections, cancer, and other immune-mediated pathologies. Particularly in cancer, cross-presentation of tumor-associated antigens is crucial for an effective antitumor CTL response. The mostly accepted cross-presentation assay is to use chicken ovalbumin (OVA) as a model antigen and then utilize OVA-specific TCR transgenic CD8+ T (OT-I) cells to measure the cross-presenting capacity. Here we describe in vivo and in vitro assays to measure the function of antigen cross-presentation using cell-associated OVA.

Thioesterase PPT1 balances viral resistance and efficient T cell crosspriming in dendritic cells.

Conventional type 1 dendritic cells (cDC1s) are inherently resistant to many viruses but, paradoxically, possess fewer acidic phagosomes that enable antigen retention and cross-presentation. We report that palmitoyl-protein thioesterase 1 (PPT1), which catabolizes lipid-modified proteins in neurons, is highly expressed in cDC1s. PPT1-deficient DCs are more susceptible to vesicular stomatitis virus (VSV) infection, and mice with PPT1 deficiency in cDC1s show impaired response to VSV. Conversely, PPT1-deficient cDC1s enhance the priming of naive CD8+ T cells into tissue-resident KLRG1+ effectors and memory T cells, resulting in rapid clearance of tumors and Listeria monocytogenes Mechanistically, PPT1 protects steady state DCs from viruses by promoting antigen degradation and endosomal acidification via V-ATPase recruitment. After DC activation, immediate down-regulation of PPT1 is likely to facilitate efficient cross-presentation, production of costimulatory molecules and inflammatory cytokines. Thus, PPT1 acts as a molecular rheostat that allows cDC1s to crossprime efficiently without compromising viral resistance. These results suggest potential therapeutics to enhance cDC1-dependent crosspriming.

Expression of LRIG1 is Associated With Good Prognosis for Human Non-small Cell Lung Cancer.

Somatic mutations, which are associated with a certain rate of response to targeted therapies, are ubiquitously found in human non-small cell lung cancer (NSCLC). However, it is largely unknown which group of patients may benefit from the respective treatments targeting different somatic mutations. Therefore, more effective prognostic and predictive markers are desperately needed for the treatment of NSCLC harboring different somatic mutations. The leucine-rich repeats and immunoglobulin-like domains (LRIG)-1 is a tumor suppressor gene that belongs to the LRIG family. LRIG1 expression has prognostic significance in various human cancers.In this study, we first used the quantitative polymerase chain reaction (qPCR) and immunohistochemical analysis of 36 and 182 NSCLC patient tissues to analyze the LRIG1 expression respectively. To investigate the prognostic value of LRIG1 in NSCLC, we examined the correlation between clinical features and overall survival (OS) with Cox proportional hazard regression. We also compared the sensitivity and specificity of LRIG1 in NSCLC prognosis by logistic regression to further evaluate the prognostic efficiency of LRIG1 in NSCLC.We found that the LRIG1 expression was associated with pathological type, differentiation status, and stage of NSCLC. The result showed that LRIG1 was an independent prognostic factor for OS of NSCLC patients. LRIG1 in combination with other clinicopathological risk factors was a stronger prognostic model than clinicopathological risk factors alone.Thus, the LRIG1 expression potentially offered a significant clinical value in directing personal treatment for NSCLC patients.