PD-L1 overexpression

This phenotypic shift is induced by the activation of the PI3K-AKT-mTOR signaling axis; thus, this study revealed a crucial regulatory mechanism that fuels tumor growth and recurrence. Importantly, targeted inhibition of the PD-L1-PI3K-AKT-mTOR signaling axis significantly suppressed the growth of AM patient-derived tumor organoids, highlighting the potential of PD-L1 blockade as a promising therapeutic approach for AM.

ICI combinations were similarly beneficial for Asian and global patients with GEA or ESCC. In conclusion, this meta-analysis, which includes unreported PD-L1 subgroups show benefit of ICIs with or without chemotherapy as a first-line treatment for advanced gastroesophageal cancers, particularly among patients with high PD-L1 expression.

T. gondii type IROP16 protein overexpression may up-regulate PD-L1 expression in A549 cells at both transcriptional and translational levels and the relative PD-L1 distribution on the A549 cell membrane surface, and affect the PD-1/PD-L1 binding in a concentration-dependent manner.

We detected variable expression of the PD-L1, PD-L2, B7-H3, B7-H4, LGALS9, and CD155 proteins in g-NENs. These results suggest that the expression level of CD155 may be a vital indicator of OS in patients with g-NENs. B7 family ligands/receptors could be potential immunotherapeutic targets for g-NENs.

Finally, competitive experiments in the presence of durvalumab are also described to study its interaction with PD-L1. This approach can also be used to study the contribution of potential conformational changes in other proteins.

Most patients received pembrolizumab (93%) and were treated with stereotactic radiation (81%)...Although high PD-L1 levels are associated with longer survival and improved intracranial control, radiation necrosis occurs more frequently in patients with high PD-L1 expression. Clinicians should be aware of long-term treatment-related toxicities in this population.

Patients with COPD were at increased risk of developing autoimmune thyroiditis compared to non-COPD patients (OR 3.9 95% CI 1.135-13.260, p = 0.0227). Our study showed that patients dealing with COPD have a 3.9 times greater risk of developing autoimmune thyroiditis as an adverse event during Pembrolizumab treatment compared with patients without COPD.

NACRT in pancreatic cancer may affect TILs and PD-L1 expression, thereby improving the immunosuppressive microenvironment and implying a potential synergy between checkpoint inhibitors and radiation treatment.

The results suggest that overexpression of PD-L1 is a risk factor for a poor prognosis in patients with GISTs. Knockdown of PD-L1 significantly inhibited the development of GISTs. PD-L1 may serve as a biomarker for the poor prognosis of GISTs and a potential therapeutic target.

Pembrolizumab together with chemotherapy improves greater survival and higher levels of response rate in patients with severe gastric cancer, especially with high PD-L1 expression. But it has rather more adverse events, allowing patient monitoring with care.

P=N/A, N=15, Recruiting, Amsterdam UMC, location VUmc | Trial completion date: Jan 2026 --> Jan 2028 | Trial primary completion date: Jan 2025 --> Jan 2027

Knocking down DNAJC8 significantly inhibited hepatocellular carcinoma cell proliferation, migration, invasion, and reduced sorafenib IC50. The seven-gene CRRG model, particularly DNAJC8, holds potential for predicting chemotherapy response and serves as a therapeutic target in hepatocellular carcinoma.

Quantification of CTCs is performed in 37 clinical samples, demonstrating results consistent with clinical diagnoses. The assay exhibits a specificity of 100% and a sensitivity of 94.5%.

To our knowledge, this is the first review assessing immunological context as biomarker for targeted therapy. The results of this review represent an important resource to aid future translational studies in advancing stratified precision medicine oncology.

BGO associates with favorable survival in patients with NSCLC receiving pembrolizumab monotherapy, but not in patients with chemo-immunotherapy or chemotherapy. Further validation of this promising strategy for personalized decision-making is warranted.

[18F]FAPI uptake was positively correlated with PD-L1 expression in lung cancer. The combination of [18F]FAPI PET/CT and PD-L1 expression may offer a more comprehensive approach to assessing the response of lung cancer to immunotherapy.

The combination therapy reverted the immunosuppressive tumor microenvironment with increased T and NKT cell infiltration. This resulted in successful treatment of advanced orthotopic tumors refractory to CAR-NK cell monotherapy.

In advanced EGFR-mutant NSCLC, high PD-L1 expression may suggest reduced efficacy of third-generation EGFR-TKIs. The spatial heterogeneity of PD-L1 expression could influence its predictive accuracy for third-generation EGFR-TKI efficacy.

Notably, αPDL1-PLG-IMDQ achieved a 97% tumor inhibition rate, prevented tumor regrowth in rechallenge experiments, and reduced lung metastases of tumors by 83%. These findings underscore its potential for intratumoral DC-targeted immunotherapy and novel systemic IMDQ and checkpoint inhibitor combinations.

18F-FDG PET/CT is effective in detecting FHRCC lesions due to their hypermetabolic nature. PET metabolic parameters can serve as predictors of positive PD-L1 expression, with higher values observed in FHRCC patients with positive PD-L1 expression. Additionally, WB-SUVpeak is a significant predictor of prognosis in patients with FHRCC.

RWE supports durvalumab's efficacy, emphasizing the need for personalized treatment strategies and further research to improve long-term outcomes.

Dabrafenib/trametinib (DT) with and without pembrolizumab and lenvatinib plus pembrolizumab (LP) were associated with higher ORR rates and improved OS and PFS. Alternatively, LP shows potential in BRAFV600 wild-type and PDL1-overexpressing cases. Routine biomarker analysis remains critical for optimising ATC management strategies.

Our CT radiomics-based LGBM model may aid in preoperatively predicting PD-L1 expression status in GC patients, and the SHAP method may improve the interpretability of this model.

The combination of isatuximab and cemiplimab demonstrated sustained antitumor activity and a manageable safety profile in R/R ENKTL. This phase II trial is registered at www.clinicaltrials.gov as #NCT04763616.

People with underlying multiple sclerosis (MS) have mostly been excluded from clinical trials of ICIs, so data on their safety in the setting of MS is limited. This report presents three clinical cases from our institution involving patients with NSCLC and pre-existing MS who were treated with ICIs.

circ_0001006 may serve as a potential prognostic predictor and therapeutic target for NSCLC. Additionally, it offers insight into a novel regulatory mechanism of circ_0001006.

P2, N=151, Active, not recruiting, Arcus Biosciences, Inc. | Trial completion date: Feb 2025 --> Aug 2025 | Trial primary completion date: Feb 2025 --> Aug 2025

The tumor-cell-intrinsic function of PD-L1 drives immunosuppression and tumor progression through the PD-L1/Jak/Stat3/IL-6/MDSC axis. This pathway represents a potential therapeutic target to improve ICI efficacy in PD-L1-high NSCLC.

These findings highlight the application of ICB to earlier stages of cancer patients. The integration of PD-L1 with BTV may immediately improve patient stratification and prediction performance in the clinic.

Our subsequent results revealed that the novel second-generation CHK1 inhibitor, prexasertib, exhibited a more pronounced inhibitory effect in MYC-overexpressed TNBC cells compared to other DNA damage repair inhibitors, including ATR, WEE1, and PARP inhibitors...In conclusion, our findings demonstrated that MYC overexpression characterizes an aggressive TNBC subtype, enabling synergistic lethality with CHK1 inhibitors. CHK1 inhibitors will be a potential therapeutic strategy in TNBC patients with MYC overexpression.

[68Ga]Ga-DOTA-PEG2-Asp2-PDL1P showed promising as a PET agent to assess tumor PD-L1 expression in preclinical and first-in-human studies, offering a non-invasive, real-time and accurate tool to address clinical challenges in predicting and assessing the efficacy of immunotherapy.

Preclinical studies that have directly compared PD-1 inhibitors support a differentiating profile associated with toripalimab compared to pembrolizumab and nivolumab with regard to their PD-1 binding sites, binding orientations, and impact on T cell function. Findings of similar or greater benefit among patients with low/no PD-L1 expression versus high/intermediate PD-L1 expression with toripalimab plus chemotherapy were also observed in advanced nasopharyngeal carcinoma and non-small cell lung cancer for both overall survival and progression-free survival. However, determination of clinically-meaningful differences between PD-1 inhibitors requires sufficiently powered head-to-head RCTs.

Samples exhibiting discordant PD-L1 IHC and/or FISH structural abnormality patterns were shown to harbor PD-L1 SV by target-capture sequencing, with positive and negative predictive values of 94% and 96%, respectively. Our approach is an alternative to target-capture sequencing for evaluating PD-L1 gene abnormalities.

Consequently, retesting for HER2 is essential in cases of recurrent UC. The association between HER2 and PD-L1 expression in high-grade, recurrent UC suggests the potential for utilizing ADC alongside immunotherapy.

These findings highlight the role of tumor-associated thrombopoiesis in generating PD-L1-expressing platelets that may serve as a resource for PD-L1-positive cells in the circulation and act as a predictive biomarker for anti-PD-1/PD-L1 therapy.

Engineered overexpression of PD-L1 in LNCaP.AR tumors resulted in resistance to PSMAxCD3 bispecific antibody treatment, whereas sensitivity was restored in combination with anti-PD-1 antibody pembrolizumab...When PSMAxCD3-treated responder mice were rechallenged with LuCaP 86.2 tumors, partial control of tumor regrowth was associated with expansion of effector memory T cells. These studies show that PSMAxCD3 treatment elicits antitumor memory T cell responses, and that combination with PD-1 blockade can enhance these effects in tumors with immune suppressive tumor microenvironments.

TLS was demonstrated to be a favorable prognostic factor in patients with UPS. Intratumoral TLS may be a biomarker for the response to ICIs, especially anti-PD-1 drugs.

Recently, immune checkpoint inhibitors using antibody drugs such as nivolumab and atezolizumab have attracted attention. Interestingly, lipid-siPDL1s strongly inhibited PD-L1 expression despite cancer cell stimulation by interferon-gamma, which induced the overexpression of PD-L1 genes. These results strongly suggest that lipid-siPDL1s could be used as novel immune checkpoint inhibitors.

Furthermore, chimeric antigen receptor (CAR)-T cell therapy and natural killer (NK) cell-based therapy targeting CSCs have achieved progress in both solid and hematologic tumors, and inhibition of CSC associated signaling pathways has proven successful. In this review, we aimed to outline the roles and regulatory mechanisms of PD-L1 in the properties of CSCs; the crosstalk between CSCs and immunosuppressive cells in TME, and recent progress and future promises of immunosuppression blockage to enhance CSC-targeted immunotherapy.

This finding reveals the epigenetic control of immune checkpoint proteins by metabolic pathways, offering a new perspective on the regulation of PD-L1. The identification of the NAMPT/SIRT1 metabolic axis as a critical factor suggests that targeting this axis may enhance therapeutic responses.

The overall TMB is increased within brain metastases compared with primary lung and other metastasis sites and is associated with a markedly diminished overall immune landscape. The identification of an immune-enriched brain metastasis subgroup suggests potential heterogeneity within the brain metastasis patient cohort, which might have implications for the development of targeted therapies.

Furthermore, the knockdown of PD-L1 mitigated the inhibitory impact of EP4 overexpression on the killing ability of CD8+ T cell and the levels of IFN-γ, IL-2, and TNF-α, all while leaving the expression of p-AKT and t-AKT unaffected. EP4 was significantly overexpressed in PCa and activated PD-L1 expression via the PI3K/AKT signaling pathway, thereby suppressing the activity of CD8+ T cells.