PD-L1 expression

P3, N=800, Recruiting, AstraZeneca | Trial primary completion date: Feb 2027 --> Nov 2026

We showed that hyperthermia increased p-STAT1 and IRF1 followed by PD-L1 expression. This study suggested that hyperthermia increased ICI through immune cell infiltration and expression of p-STAT1 and IRF1 pathways.

Comprehensive serum biomarker analysis revealed that a lower fold change in serum IL-8 was associated with better outcomes in pre-treated patients with advanced NSCLC receiving atezolizumab.

This study provides data on the molecular epidemiology of lung adenocarcinoma in Brazil, confirming high prevalence of EGFR mutations, ALK fusions, and MET exon 14 skipping alteration. Biomarker detection is largely affected by biospecimen collection and processing, with one third of the patients eligible for non-NGS testing only, which presents reduced coverage and sensitivity for actionable drivers.

The study concluded that the PD-L1 expression scoring system effectively discriminates between patients with breast cancer in terms of the degree of benefit they may attain from ICIs. Patients with little or no PD-L1 expression experienced a diminished therapeutic benefit from ICIs.

The efficacy of post-relapse EGFR-TKI treatment was independent of PD-L1 expression. The significance of PD-L1 expression in perioperative EGFR-TKI therapy should be evaluated.

P2, N=179, Completed, Hoffmann-La Roche | Active, not recruiting --> Completed

Furthermore, the knockdown of IRF1 impaired the induction of PD-L1 expression in CCS cells. Therefore, the inhibition of HDAC1/3 has potential as a novel strategy to increase immunogenicity and as combination therapy with ICIs for CCS and melanoma.

Finding and confirming these biomarkers is essential for improving early detection, tracking the course of the disease, and directing focused treatments. As research progresses, combining molecular, genetic, and environmental insights might improve lung cancer care, prevention, and early diagnosis, thereby lowering the disease's worldwide burden.

In advanced gastric cancer, reduced peripheral blood MDSC and Treg levels postchemotherapy and negative PD-1 and PD-L1 expression in tissues are associated with improved chemotherapy efficacy and are independent prognostic factors for PFS and OS.

High CD64 expression was also correlated with increased serum CRP levels. The CRP-CD64 signal was linked to the protumor activation of TAMs and could be a promising target for anticancer immunotherapy in ccRCC.

According to ML models specific gut microbiome MTR signatures' associate with ICI treated NSCLC outcomes. Specific gene clusters and taxa MTR gene expression might differentiate long vs short PFS.

We observed that OC clinical and pathological characteristics of these patients from Tunisia were similar to those of Caucasian patients. We identified frequent CNA in this population that need to be confirmed in other sets from Africa.

P2, N=100, Recruiting, Nanfang Hospital, Southern Medical University | Trial completion date: Jul 2024 --> Sep 2027 | Trial primary completion date: Mar 2023 --> Jun 2025

Importantly, the immune checkpoint blockade effect of TIN can enhance the immune response of PDT-induced ICD for metastatic tumor treatment. This study presents a self-assembling strategy for the development of an all-in-one nanomedicine, effectively integrating multiple therapeutic modalities to provide a comprehensive and systemic approach for tumor suppression.

Our study demonstrated that the therapeutic effect of anti-angiogenic treatment after immune checkpoint therapy was superior to that of concurrent therapy, whereas anti-angiogenic therapy followed by immunotherapy did not bring more significant clinical benefits than independent monotherapy.

This single-cell analysis builds upon our understanding of the impact of Ad-IFNα on tumor cells and other compartments of the microenvironment. These data will help identify mechanisms to improve patient selection and therapeutic efficacy of Nadofaragene firadenovec.

The proposed AI-based algorithm accurately predicted the survival of each patient with advanced NSCLC. The AI-based methodology will contribute to personalized medicine.

Furthermore, the result showed that the number of FGFBP2(+) Tm cells in metastases was positively correlated with the number of vessels in liver/lung metastases. In conclusion, we confirmed that the expression of PD-L1 in primary tumor can increase the number of FGFBP2(+) Tm cells in peripheral blood and promote tumor metastasis, which is likely to be caused by the angiogenesis of FGFBP2(+) Tm cells in metastases.

Phase III clinical evaluation of enlonstobart for use as first-line treatment (in combination with chemotherapy ± bevacizumab) in patients with recurrent or metastatic PD-L1-positive cervical cancer is also underway in China. Additionally, phase II clinical development of enlonstobart (as a part of combination therapy) for use against a range of other solid tumour types is continuing. This article summarises the milestones in the development of enlonstobart leading to this first approval for recurrent or metastatic cervical cancer.

OMPP-mediated therapy has been shown to provoke robust immune responses to suppress B16-OVA melanoma and prevent postsurgical tumor recurrence. This work presents a facile strategy for the fabrication of nanovaccines by integrating carrier and adjuvant while exploring the inherent properties to promote antigen release and modulate immunosuppression, which demonstrates great potential for effective cancer immunotherapy.

We demonstrated that FOXA1 prevents tumor immune evasion by inhibiting IFN-γ induced PD-L1 expression in NPC cells. Our research findings provide new insights into the immunotherapeutic biomarkers and targets for NPC, which is important for the clinical application of programmed cell death protein-1/PD-L1 antibodies in NPC.

Our results confirm the positive impact of immunotherapy in real-world conditions and show different effects of PD-L1 expression level on patients' survival depending on sex and histology. Determination of different PD-L1 expression breaking points in males and females with NSCLC is a solid starting point for more research on this topic.

The presence of ≥ 6% PD-L1 (CD274) tumoral expression was found to be significantly associated with 2-year overall survival (OS), locoregional recurrence (LRC), distant metastasis (DM), and various clinicopathological parameters. Tumoral PD-L1 was found as a discrete prognostic biomarker which showed significant association with tumor aggressiveness.

Our study shows that CTLA-4 is a more important immune checkpoint regulator in breast carcinomas in comparison to PD-L1. Thus, anti-CTLA-4 immunotherapy might prove to be of immense help in the treatment of invasive ductal carcinoma breast showing overexpression of CTLA-4.

In the Korean cohort, ICIs were most effective in MSI and EBV cases, showing disease control rates of 100%, compared to 62.9% in GS and 12.5% in CIN subtypes. The NGS method successfully maps the mutational landscape of GC, providing a practical TCGA classification surrogate to optimize patient-specific treatment strategies.

This study uncovers a novel mechanism for the coordinated translational regulation of the PD- L1/PD1 and CD155/TIGIT immune checkpoint pathways and highlights the ISR as a therapeutic vulnerability for lung cancer. Inhibition of the ISR pathway bolsters PD-1 blockade, potentially unveiling a new therapeutic strategy for lung cancer patients.

Combined evaluation of eosinophil count and PD-L1 expression may enhance personalized treatment strategies. Further validation in prospective, randomized studies is necessary.

There is no evidence that perioperative immunotherapy is better than neoadjuvant immunochemotherapy in EFS. Patients with non-squamous disease, PD-L1 expression more than 50%, or stage III disease can try the neoadjuvant immunochemotherapy mode.

We developed a novel new squamous cell lung carcinoma cell line, OMUL-1, that expresses IGF1R and PD-L1.

These findings indicate that the TRPM family-particularly CCNE1, which is associated with TRPM-is a significant player in the pan-cancer domain and can be utilized as a therapeutic target and prognostic biomarkers, especially in immuno-oncology. The thorough characterization of the TRPM family and the discovery of CCNE1 as a crucial downstream effector mark important developments in our comprehension of pan-cancer biology.

Treatment with the KRasG12C-specific inhibitor, ARS-1620, significantly increased IDO1 expression, which inversely correlated with PD-L1 expression in the KRasG12C-mutant H358 cell line...Moreover, the induction of IDO1 expression following KRas inhibition appears to operate independently of the MAPK pathway. Our results propose that concurrent targeting of KRas and IDO1 could potentiate therapeutic efficacy in KRas-mutant cancers, overcoming resistance to immune checkpoint blockade.

Furthermore, silencing YAP or treating with its inhibitor, Verteporfin, attenuated PD-L1 expression induced by Gq/G11 mutations, thereby enhancing T cell activation and T cell-mediated cytotoxicity. Collectively, this study reveals a potential role of Gq/G11 mutations on immune evasion of UM, a new mechanism of Gq/11 mutations-induced tumorigenesis, highlighting Gq/G11 and YAP as potential immunotherapeutic targets and suggesting Verteporfin as an adjuvant for immunotherapy of UM patients with GNAQ or GNA11 mutations.

The results of our study are highly encouraging, as they revealed a significant correlation between immunohistochemical biomarkers, therapeutic regimens, and prognosis. These findings indicate that our immunohistochemical detection panel has great potential for facilitating customization of therapeutic regimens to improve patient care. The insights gained from this study could help clinicians optimize treatment protocols and ultimately enhance clinical outcomes.

Kupffer cells also produced decreased IL-6 and IL-18 level and upregulated IL-10 level after co-culture with MDSCs. This study provides insights into the potential targets and mechanisms of Rg3 in HCC and lays a foundation for personalized treatment strategies.

Programmed cell death-ligand 1 (PD-L1) clone 22C3 is the only Food and Drug Administration-approved companion diagnostic test for pembrolizumab for the treatment of esophageal squamous cell carcinoma (ESCC)...We performed a comprehensive study to investigate the expression profile of PD-L1 clone 22C3 in the US patients with ESCC. Our analysis showed that PD-L1 (22C3) expression decreased in treated specimens, and a CPS of ≥25 was associated with a favorable prognosis.

The SNAs@CCMR consisted of antisense oligonucleotides grafted gold nanoparticles (SNAs) as core and TLR7 agonist imiquimod (R837) functionalized cancer cell membrane (CCM) as shell, in which the acid-labile Schiff base bond was used to connect the R837 and CCM...These chain processes not only damaged the primary tumor, but also produced plenty of tumor-associated antigens, which matured the surrounding dendritic cells (DCs) and activated anti-tumor T cells along with the released R837, resulting in the enhanced immunotherapy with suppressive immune escape. Both in vivo and in vitro experiments demonstrated that our nanoparticles were able to inhibit primary tumor and its metastasis via multi-regulation of carcinogenic microRNAs and RNAs dependent photothermal-immune activations, which provided a promising strategy to reprogram the immunosuppressive microenvironment in tumor tissue for better malignant tumor therapy.

P2, N=114, Active, not recruiting, Sun Yat-sen University | Recruiting --> Active, not recruiting | Trial primary completion date: Jul 2025 --> Nov 2025

P2, N=143, Active, not recruiting, Astellas Pharma Global Development, Inc. | Recruiting --> Active, not recruiting

Importantly, LA treatment synergized with PD-1 antibody and overcame immune checkpoint blockade (ICB) resistance, which likely resulted from nPD-L1-increased MHC-I expression and sensitivity of tumor cells to interferon-γ. These findings offer a conceptual advance for PD-L1 function and suggest LA as a promising therapeutic option for overcoming ICB resistance.

OS subgroup analysis showed comparable treatment effect by TAP score at 10% cutoff, CPS at cutoff 10, and TC score at 1% cutoff. TAP score and CPS at these cutoffs exhibited substantial concordance. Results indicate that the quicker, visually estimated TAP score and CPS may be interchangeable for clinical measurement of PD-L1 expression in patients with ESCC.

We performed a comprehensive evaluation of liver-metastatic (LM) disease among mCRC patients enrolled in the phase II randomized AtezoTRIBE trial, that showed a modest benefit from the addition of atezolizumab (atezo) to 1st line FOLFOXIRI/bevacizumab (bev) and identified Immunoscore IC as a predictor of ICI efficacy in the proficient mismatch repair (pMMR) population... In our cohort of pMMR mCRC patients, the immune microenvironment of tumors with LM spread does not differ from that of tumors with no liver involvement. The presence or not of LM disease does not affect the efficacy of adding atezo to first-line FOLFOXIRI/bev, differently than Immunoscore IC.