Programmed Cell Death Ligand 1 Protein Research Articles

PD-L1 protein expression in breast cancer

AimsThe immune checkpoint marker, Programmed cell death-ligand 1 (PD-L1), is expressed by both cancer epithelial cells and tumour-infiltrating immune cells (TICs) thus constituting a potential target for immunotherapy. This is...

Targeting VPS18 hampers retromer trafficking of PD-L1 and augments immunotherapy.

Immune checkpoint inhibitors targeting programmed cell death 1 (PD-1) or programmed cell death-ligand 1 (PD-L1) have achieved impressive antitumor clinical outcomes. However, the limited response rates suggest the incomplete understanding of PD-L1 regulation. Here, we demonstrate that vacuole protein sorting 11 and 18 (VPS11/18), two key players in vesicular trafficking, positively regulate PD-L1 and confer resistance to immune checkpoint blockade therapy. VPS11/18 interact with PD-L1 in endosome recycling accompanied by promoting PD-L1 glycosylation and protein stability. VPS18 deficiency enhances antitumor immune response. Pharmacological inhibition by VPS18 inhibitor RDN impaired PD-L1 member trafficking and protein stability. Combination treatment of RDN and anti-cytotoxic T lymphocyte-associated antigen 4 synergistically enhances antitumor efficacy in aggressive and drug-resistant tumors. RDN exerted lung-preferred distribution and good bioavailability, suggesting a favorable drug efficacy. Together, our study links VPS18/11-mediated trans-Golgi network recycling of PD-L1 and points to a promising treatment strategy for the enhancement of antitumor immunity.

Prognostic Significance of Programmed Cell Death-Ligand 1 Expression in Tobacco Associated Oral Squamous Cell Carcinoma: An Immunohistochemical Based Cross-Sectional Study.

Advancements in immuno-oncology have dramatically transformed cancer treatment. Immunotherapy, targeting immune check point proteins, notably Programmed cell death ligand 1 (PD-L1) and its receptor Programmed Cell Death-1 (PD-1) which modulate the activity of immune response in Head and Neck squamous cell carcinomas (HNSCC), is an area of much research. The immunohistochemical expression of PD-L1 in cancer cells has been proposed as a predictive biomarker for selecting candidates for immunotherapy. Thus, the present study was undertaken to study the expression of PD-L1 in the primary tumour cells and evaluate its correlation with various clinicopathological parameters and prognosis in tobacco associated oral squamous cell carcinomas (OSCC). Expression of PD-L1 was investigated in 75 surgically resected cases of OSCC by immunohistochemistry and its association with different clinicopathological features and prognosis was analysed. PD-L1 protein was detected in 68% (51 cases) of cases. Tumour stage (p = 0.04), lymph node (LN) metastasis (p < 0.01) and moderate to marked tumour infiltrating lymphocytes (TILs) (p < 0.05), significantly correlated with the PD-L1 expression in the primary tumour. PD-L1 expression did not show a significant association with overall survival (OS) rate, however, patients with positive PD-L1 expression showed a poorer survival rate. Patients exhibiting nodal positivity had the worst prognosis (p < 0.005). These data demonstrated a significant association of ≥ 5% PD-L1 expression in the primary tumour and the presence of LN metastasis, moderate to marked TILs and advancing tumour stage, thus, making it a plausible immunotherapeutic target molecule in OSCC patients.

CD38 symmetric dimethyl site R58 promotes malignant tumor cell immune escape by regulating the cAMP-GSK3β-PD-L1 axis

In recent years, immunotherapy has emerged as an effective approach for treating tumors, with programmed cell death ligand 1 (PD-L1)/programmed cell death protein-1 (PD-1) immune checkpoint blockade (ICB) being a promising strategy. However, suboptimal therapeutic efficacy limits its clinical benefit. Understanding the regulation mechanism of PD-L1 expression is crucial for improving anti-PD-L1/PD-1 therapy and developing more effective tumor immunotherapy. Previous studies have revealed that resistance to PD-L1/PD-1 blockade therapy arises from the upregulation of CD38 on tumor cells induced by ATRA and IFN-β, which mediates the inhibition of CD8+ T cell function through adenosine receptor signaling, thereby promoting immune evasion.Yet, the precise role of CD38 in regulating PD-L1 on malignant tumor cells and its impact on CD8+ T cells through PD-L1 remain unclear. Here, we demonstrate that CD38 is highly expressed in malignant tumors (lung cancer, nasopharyngeal carcinoma, cervical cancer) and upregulates PD-L1 protein expression, impairing CD8+ T cell function. Mechanistically, CD38 phosphorylates GSK3β via the adenosine-activated cAMP-PKA signaling pathway, leading to GSK3β inactivation and enhanced PD-L1 stability and expression, facilitating tumor immune escape. Furthermore, we identify PRMT5 as a novel CD38-interacting molecule that symmetrically dimethylates CD38 arginine position 58, augmenting PD-L1 stability and expression through the ADO-cAMP-GSK3β signaling axis. This inhibits CD8+ T cell-mediated tumor cell killing, enabling tumor cells to evade immune surveillance. Our findings suggest that targeting the CD38 R58 site offers a new avenue for enhancing anti-PD-L1/PD-1 therapy efficacy in tumor treatment.

German expert consensus on programmed cell death ligand1 (PD-L1) testing in perioperative systemic therapy of muscle invasive bladder cancer

The risk of recurrence in patients with muscle invasive bladder cancer (MIBC) after radical cystectomy depends on the pathological tumor stage. In particular, patients with lymph node metastasis (pN+), locally advanced (≥pT3), or residual muscle invasive tumor despite neoadjuvant chemotherapy are at high risk. Currently, the importance of adjuvant therapy with immune checkpoint inhibitors is increasing in the context of perioperative systemic therapeutic concepts. The indication for the PD‑1 inhibitor nivolumab currently approved in the European Union requires testing of PD-L1 (programmed cell death ligand1) protein expression by immunochemistry in tumor tissue. Focusing on MIBC patients at high risk of recurrence, new questions arise regarding the implementation and interpretation of PD-L1 testing. An interdisciplinary group of experts from Germany has discussed relevant issues from aclinicopathological point of view and developed practical recommendations to facilitate the implementation of validated and quality-assured PD-L1 testing for the approved indications in daily clinical practice.

Nearly Half of Patients with Anaplastic Thyroid Cancer May Be Amenable to Immunotherapy.

Poorly differentiated cancer (PDC) and anaplastic thyroid cancer (ATC) have an aggressive course of disease with limited treatment options. The expression of programmed cell death ligand-1 (PD-L1) has been used to determine the responses of many cancers to immunotherapy. The aim of the study was to investigate the expression of PD-L1 in a cohort of patients with PDC and ATC to assess their suitability for immunotherapy. Data, settings, and participants: This study is a retrospective cohort review of patients treated for PDC and ATC treated at a tertiary referral institution during the period 2000-2020. PD-L1 22C3 pharmDx qualitative immunohistochemistry was performed on formalin-fixed, paraffin-embedded (FFPE) specimens of tumours to detect the presence of the PD-L1 protein. The percentage of tumours that were positive for PD-L1 immunohistochemistry and the PD-L1 protein expression as measured by using the Tumour Proportion Score (TPS). Secondary outcomes studied were the associations between demographic, clinicopathological, treatment and disease outcomes and PD-L1 expression. Nineteen patients (12F:7M) with a mean age of 65.4 (±14.3 SD) years were diagnosed with PDC in 4 (21%) and fifteen were diagnosed with ATC (79%) during the study period. Fifteen (79%) patients underwent some form of surgery, with R0 resection achieved in only three of the fifteen (20%) patients. Overall, PD-L1 expression was seen in seven of the fifteen (47%) of the patients with ATC, with no positivity seen in the patients with PDC. PD-L1 expression had no impact on treatment modality and positive expression was not significantly associated with stage of disease, metastasis, or survival. Nearly half of patients with ATC express PD-L1 and may be amenable to immunotherapy with pembrolizumab.

PD-1/PD-L1 Provides Protective Role in Hypoxia-Induced Pulmonary Vascular Remodeling.

Hypoxia-induced pulmonary hypertension (HPH) is a T helper 17 cell response-driven disease, and PD-1 (programmed cell death 1)/PD-L1 (programmed cell death-ligand 1) inhibitor-associated pulmonary hypertension has been reported recently. This study is designed to explore whether the PD-1/PD-L1 pathway participates in HPH via regulating endothelial dysfunction and T helper 17 cell response. Lung tissue samples were obtained from eligible patients. Western blotting, immunohistochemistry, and immunofluorescence techniques were used to assess protein expression, while immunoprecipitation was utilized to detect ubiquitination. HPH models were established in C57BL/6 WT (wild-type) and PD-1-/- mice, followed by treatment with PD-L1 recombinant protein. Adeno-associated virus vector delivery was used to upregulate PD-L1 in the endothelial cells. Endothelial cell function was assessed through assays for cell angiogenesis and adhesion. Expression of the PD-1/PD-L1 pathway was downregulated in patients with HPH and mouse models, with a notable decrease in PD-L1 expression in endothelial cells compared with the normoxia group. In comparison to WT mice, PD-1-/- mice exhibited a more severe HPH phenotype following exposure to hypoxia, However, administration of PD-L1 recombinant protein and overexpression of PD-L1 in lung endothelial cells mitigated HPH. In vitro, blockade of PD-L1 with a neutralizing antibody promoted endothelial cell angiogenesis, adhesion, and pyroptosis. Mechanistically, hypoxia downregulated PD-L1 protein expression through ubiquitination. Additionally, both in vivo and in vitro, PD-L1 inhibited T helper 17 cell response through the PI3K (phosphoinositide 3-kinase)/AKT (protein kinase B)/mTOR (mammalian target of rapamycin) pathway in HPH. PD-1/PD-L1 plays a role in ameliorating HPH development by inhibiting T helper 17 cell response through the PI3K/AKT/mTOR pathway and improving endothelial dysfunction, suggesting a novel therapeutic indication for PD-1/PD-L1-based immunomodulatory therapies in the treatment of HPH.

Differential Expression of CKLF-like MARVEL Transmembrane Domain-Containing Protein 6 and Programmed Cell Death Ligand 1 as Prognostic Biomarkers in Upper Tract Urothelial Carcinoma.

Upper tract urothelial carcinoma (UTUC) accounts for 5-10% of all UCs. Immune checkpoint inhibitors (ICIs) have been established for UCs. The prognostic and predictive potential of programmed cell death ligand 1 (PD-L1) expression to stratify patients benefiting from ICIs is not fully understood, and additional markers influencing the impact of PD-L1-mediated ICI response are needed. Previously, the chemokine-like MARVEL transmembrane domain-containing protein 6 (CMTM6) was identified as a positive regulator of PD-L1. Our aim was to investigate the expression profiles and impact of PD-L1 and CMTM6 protein status on the prognostic parameters and survival of UTUC patients. In this retrospective study, the combined positive score (CPS), tumor proportion score (TPS), and immune cell score (ICS) for PD-L1 and CMTM6 were determined. High PD-L1 CPS, ICS, and TPS were found in 77.4%, 58.3%, and 45.2% of cases, and high CMTM6 CPS, ICS, and TPS were seen in 52.5%, 51.5%, and 55.5% of cases, respectively. The scores of both markers had a significant positive correlation. High PD-L1 and CMTM6 expression was coupled with higher pT status, WHO grade, necrosis, and metastasis (p < 0.05, respectively). In the univariate survival analysis, patients with a PD-L1 ICS high and higher degree of intratumoral inflammation showed significantly longer overall survival. Compared to other studies on UC, our study shows a substantially higher rate of PD-L1-positive tumors. CMTM6 was associated with more aggressive tumors.

Expression and correlation of PD-L1 and HER2 in oesophageal squamous cell carcinoma

AimsIn recent years, patients with programmed cell death-Ligand 1 (PD-L1)-positive oesophageal squamous cell carcinoma (OSCC) have been able to benefit from immunotherapy. However, method for improving the treatment efficacy of...

Evaluation of PDL1 positive cancer cell-specific binding activity of recombinant anti-PDL1 scFv.

Programmed cell death-ligand 1 (PDL1) is a transmembrane protein that is characterized as an immune regulatory molecule. We recently developed a recombinant single-chain fragment of variable domain (scFv) against PDL1, which showed high binding efficiency to purified recombinant PDL1 protein. However, at that time, proof-of-concept data for the effect of scFv using PDL1-expressing cells was lacking. In this study, we conducted two kinds of cell-based immunoassays, western blotting and enzyme-linked immunosorbent assay, using anti-PDL1 scFv. The results indicate that scFv can selectively and sensitively detect PDL1 from PDL1 positive human cancer cell lines. Our findings suggest that scFv could be used as a potential PDL1 inhibitor agent and probe for cell-based immunoassays to detect PDL1.

A self-assembly active nanomodulator based on berberine for photothermal immunotherapy of breast cancer via dual regulation of immune suppression

Breast cancer (BC) remains a significant global health concern, especially affecting women, necessitating the development of effective treatment strategies. Photothermal immunotherapy has holds promise for addressing BC by eradicating tumors, preventing metastasis, and reducing recurrence rates. However, the dynamic amplification of indoleamine 2,3-dioxygenase 1 (IDO-1) and programmed cell death-ligand 1 (PD-L1) triggered by photothermal therapy (PTT) poses presents a significant barrier to immune cell infiltration, thus promoting immune evasion. To enhance overall efficiency, a hyaluronic acid (HA)-coated berberine (BBR)-indocyanine green self-assembly active nano modulator (HBI NDs) was successfully developed. This nano modulator aims to reverse immune resistance and further contribute to the synergistic anti-tumor effects. The prepared HBI NDs demonstrated a uniform spherical morphology, high drug loading, and favorable optical properties. The results based on in vitro cell experiments and tumor animal models confirmed that HBI NDs selectively accumulated in tumor tissues, downregulated PD-L1 and IDO-1 protein expression, and induced elevated cell apoptosis. Consequently, these effects result in efficient immune infiltration and positive anti-tumor outcomes. In conclusion, the HBI NDs nanodrug exhibits considerable potential as a novel agent for enhancing anticancer efficacy and promoting immune infiltration.

Predictions of Programmed Cell Death Ligand 1 Blockade Therapy Success in Patients with Non-Small-Cell Lung Cancer

Lung cancer is responsible for the most cancer deaths worldwide, with non-small-cell lung cancer (NSCLC) making up 80% of cases. Some genetic factors leading to NSCLC development include genetic mutations and Programmed Cell Death Ligand 1 (PD-L1) expression. PD-L1 proteins are targeted in an NSCLC treatment called PD-L1 blockade therapy (immune therapy). However, this treatment is effective in a low percentage of patients. This study aimed to create machine learning models to use features, like the number of mutations and the number of PD-L1 proteins in cancer cells, along with others, to predict whether a patient will receive clinical benefits from immune therapy. This was carried out by downloading and merging datasets from cbioportal.org to create a sample size for the model. Features that were highly correlated with clinical benefits were identified. Three machine learning models (Gaussian naïve Bayes, decision tree, and logistic regression) were created using these features to predict clinical benefits in patients, and each model’s accuracy was evaluated. All three models had accuracy rates between 55 and 85%, with two of the models averaging an accuracy rate of around 75%. Doctors can use these models to more accurately predict whether immune therapy treatment is likely to work in a patient before prescribing it to them.

CDK5 destabilizes PD-L1 via chaperon-mediated autophagy to control cancer immune surveillance in hepatocellular carcinoma

BackgroundIn the past few years, immunotherapies of hepatocellular carcinoma (HCC) targeting programmed cell death protein 1 (PD-1) and its ligand programmed cell death ligand 1 (PD-L1), have achieved durable clinical...

A Comparative Study of Antitumor Immunity Induced by Radiofrequency Microwave and Cryoablation in Hepatocellular Carcinoma.

This study aimed to compare the immune responses induced by microwave ablation (MWA), radiofrequency ablation (RFA), and cryoablation (CRYO) in hepatocellular carcinoma (HCC) and identify differences in immune responses and the timing of immune changes. A bilateral subcutaneous model was established in C57 mice, and the successfully modeled mice were divided into the microwave (n = 15), radiofrequency (n = 15), CRYO (n = 15), control (n = 9), and blank groups (n = 3). Mice in the control group were dissected before ablation, whereas mice in the three ablation groups underwent ultrasound-guided ablation of one axillary tumor. Three mice were sacrificed and dissected at 1-4 weeks after ablation. After tissue processing, flow cytometry was used to detect the levels of CD8 + T and regulatory T (Treg) cells in the tissue, and western blotting was used to assess the level of programmed cell death ligand 1 (PD-L1) protein in the tumor tissue. The pattern of immune changes after the three types of ablation was consistent, with immune changes occurring at 3-4 weeks. CRYO induced the most significant increase in the percentage of CD8 + T cells. There were no significant differences in the levels of Treg cells and the level of PD-L1 protein among the three types of ablation (p > 0.05), but the decline in Treg cells and PD-L1 protein level caused by CRYO was the most pronounced. In the HCC mouse model, the immune changes following the three types of ablation were consistent, with immune changes occurring at 3-4 weeks. Among them, CRYO elicited the strongest adaptive immune response, and RFA outperformed MWA.

Novel quantitative immunohistochemical analysis for evaluating PD-L1 expression with phosphor-integrated dots for predicting the efficacy of patients with cancer treated with immune checkpoint inhibitors.

Programmed cell death ligand 1 (PD-L1) expression in tumor tissues is measured as a predictor of the therapeutic efficacy of immune checkpoint inhibitors (ICIs) in many cancer types. PD-L1 expression is evaluated by immunohistochemical staining using 3,3´-diaminobenzidine (DAB) chronogenesis (IHC-DAB); however, quantitative and reproducibility issues remain. We focused on a highly sensitive quantitative immunohistochemical method using phosphor-integrated dots (PIDs), which are fluorescent nanoparticles, and evaluated PD-L1 expression between the PID method and conventional DAB method. In total, 155 patients with metastatic or recurrent cancer treated with ICIs were enrolled from four university hospitals. Tumor tissue specimens collected before treatment were subjected to immunohistochemical staining with both the PID and conventional DAB methods to evaluate PD-L1 protein expression. PD-L1 expression assessed using the PID and DAB methods was positively correlated. We quantified PD-L1 expression using the PID method and calculated PD-L1 PID scores. The PID score was significantly higher in the responder group than in the non-responder group. Survival analysis demonstrated that PD-L1 expression evaluated using the IHC-DAB method was not associated with progression-free survival (PFS) or overall survival (OS). Yet, PFS and OS were strikingly prolonged in the high PD-L1 PID score group. Quantification of PD-L1 expression as a PID score was more effective in predicting the treatment efficacy and prognosis of patients with cancer treated with ICIs. The quantitative evaluation of PD-L1 expression using the PID method is a novel strategy for protein detection. It is highly significant that the PID method was able to identify a group of patients with a favorable prognosis who could not be identified by the conventional DAB method.

ANXA1 promotes tumor immune evasion by binding PARP1 and upregulating Stat3-induced expression of PD-L1 in multiple cancers.

The deregulation of annexin A1 (ANXA1), a regulator of inflammation and immunity, leads to cancer growth and metastasis. However, whether ANXA1 is involved in cancer immunosuppression is still unclear. Here, we report that ANXA1 knockdown (i) dramatically downregulates programmed cell death-ligand 1 (PD-L1) expression in breast cancer, lung cancer, and melanoma cells; (ii) promotes T cell-mediated killing of cancer cells in vitro; and (iii) inhibits cancer immune escape in immune-competent mice via downregulating PD-L1 expression and increasing the number and killing activity of CD8+ T cells. Mechanistically, ANXA1 functioned as a sponge molecule for interaction of PARP1 and Stat3. Specifically, binding of ANXA1 to PARP1 decreased PARP1's binding to Stat3, which reduced poly(ADP-ribosyl)ation and dephosphorylation of Stat3 and thus, increased Stat3's transcriptional activity, leading to transcriptionally upregulated expression of PD-L1 in multiple cancer cells. In clinical samples, expression of ANXA1 and PD-L1 was significantly higher in breast cancer, non-small cell lung cancer, and skin cutaneous melanoma compared to corresponding normal tissues and positively correlated in cancer tissues. Moreover, using both ANXA1 and PD-L1 proteins for predicting efficacy of anti-PD-1 immunotherapy and patient prognosis were superior to using individual proteins. Our data suggest that ANXA1 promotes cancer immune escape via binding PARP1 and upregulating Stat3-induced expression of PD-L1, that ANXA1 is a potential new target for cancer immunotherapy, and combination of ANXA1 and PD-L1 expression is a potential marker for predicting efficacy of anti-PD-1 immunotherapy in multiple cancers.

Assessment of Programmed Cell Death Ligand-1 Expression in Non-small Cell Lung Carcinomas by Immunohistochemistry

Background: Non-small cell lung carcinomas (NSCLCs) expressing programmed cell death ligand-1 (PD-L1), a transmembrane protein, are more likely to respond to immunotherapy drugs. All advanced NSCLC samples should be examined with PD-L1 immunohistochemistry (IHC). PD-L1 is now the only approved predictive biomarker of immunotherapy response in NSCLC patients. This study evaluates the expression of PD-L1 in NSCLC by IHC and assesses the morphological and clinical correlation of PD-L1 expression. Materials and Methods: All patients with histologically proven NSCLC with needle core biopsies and resected specimens were analyzed in the department of pathology. The correlation of PD-L1 expression with morphological and clinical parameters was analyzed. Results: On evaluating PD-L1 expression in 97 cases of NSCLC, 61.85% ( n = 60) had positive PD-L1 staining. Among patients with a positive tumor proportion score, 22 had a history of smoking, 51 were ≥50 years old, 43 were male patients, 24 were in Stage IV, 44 had a history of chemotherapy or radiotherapy, 47 had adenocarcinoma, and 33 had Grade II tumors. The association of PD-L1 expression with various clinicopathological parameters such as gender, smoking status, histological type, histological grade, clinical tumor stage, previous treatment history, site and type of biopsy, necrosis, and peritumoral lymphoid response was not statistically significant. Conclusion: Our study indicated that PD-L1 expression was not associated with various clinicopathological variables in NSCLC. More research is needed to look into the probable factors that influence the PD-L1-positive distribution. Since expression of the PD-L1 protein is proven to be of therapeutic and prognostic significance, we recommend that testing for PD-L1 should be done at least in cases of advanced-stage NSCLC.

Anti-Proliferative Effect of Radiotherapy and Implication of Immunotherapy in Anaplastic Thyroid Cancer Cells.

Radiotherapy and immunotherapy have shown promising efficacy for the treatment of solid malignancies. Here, we aim to clarify the potential of a combined application of radiotherapy and programmed cell death-ligand 1 (PD-L1) monoclonal antibody atezolizumab in primary anaplastic thyroid cancer (ATC) cells. The radiation caused a significant reduction in cell proliferation, measured by luminescence, and of the number of colonies. The addition of atezolizumab caused a further reduction in cell proliferation of the irradiated ATC cells. However, the combined treatment did not cause either the exposure of the phosphatidylserine or the necrosis, assessed by luminescence/fluorescence. Additionally, a reduction in both uncleaved and cleaved forms of caspases 8 and 3 proteins was detectable in radiated cells. The DNA damage evidenced the over-expression of TP53, CDKN1A and CDKN1B transcripts detected by RT-qPCR and the increase in the protein level of P-γH2AX and the DNA repair deputed kinases. PD-L1 protein level increased in ATC cells after radiation. Radiotherapy caused the reduction in cell viability and an increase of PD-L1-expression, but not apoptotic cell death in ATC cells. The further combination with the immunotherapeutic atezolizumab could increase the efficacy of radiotherapy in terms of reduction in cell proliferation. Further analysis of the involvement of alternative cell death mechanisms is necessary to clarify their cell demise mechanism of action. Their efficacy represents a promising therapy for patients affected by ATC.

B4GALT1 promotes immune escape by regulating the expression of PD-L1 at multiple levels in lung adenocarcinoma

BackgroundInvasive adenocarcinoma (IAC), which is typically preceded by minimally invasive adenocarcinoma (MIA), is the dominant pathological subtype of early-stage lung adenocarcinoma (LUAD). Identifying the molecular events underlying the progression from MIA to IAC may provide a crucial perspective and boost the exploration of novel strategies for early-stage LUAD diagnosis and treatment.MethodsTranscriptome sequencing of four pairs of MIA and IAC tumours obtained from four multiple primary lung cancer patients was performed to screen out beta-1,4-galactosyltransferase1 (B4GALT1). Function and mechanism experiments in vitro and in vivo were performed to explore the regulatory mechanism of B4GALT1-mediated immune evasion by regulating programmed cell death ligand 1 (PD-L1).ResultsB4GALT1, a key gene involved in N-glycan biosynthesis, was highly expressed in IAC samples. Further experiments revealed that B4GALT1 regulated LUAD cell proliferation and invasion both in vitro and in vivo and was related to the impaired antitumour capacity of CD8 + T cells. Mechanistically, B4GALT1 directly mediates the N-linked glycosylation of PD-L1 protein, thus preventing PD-L1 degradation at the posttranscriptional level. In addition, B4GALT1 stabilized the TAZ protein via glycosylation, which activated CD274 at the transcriptional level. These factors lead to lung cancer immune escape. Importantly, inhibition of B4GALT1 increased CD8 + T-cell abundance and activity and enhanced the antitumour immunity of anti-PD-1 therapy in vivo.ConclusionB4GALT1 is a critical molecule in the development of early-stage LUAD and may be a novel target for LUAD intervention and immunotherapy.

Circ-0000512 inhibits PD-L1 ubiquitination through sponging miR-622/CMTM6 axis to promote triple-negative breast cancer and immune escape

BackgroundThis study reported the function and mechanism of circ-0000512 in the progression of triple-negative breast cancer (TNBC).Methodscirc-0000512 expression in TNBC tissues and paired adjacent normal tissues and cells was examined...