PD-1-L

P2, N=24, Recruiting, Ever Supreme Bio Technology Co., Ltd. | Trial completion date: Dec 2023 --> Dec 2026 | Trial primary completion date: Dec 2022 --> Dec 2026

Cell counting kit-8 assay showed that PDP1 overexpression significantly raised MDA-MB-231 and MCF7 cell viability while STAT3 inhibitor S3I-201 recovered the cell growth to normal level. To summarize, PDP1 promotes the progression of BC through STAT3 pathway by regulating p-STAT3. The findings contribute to understanding the molecular mechanisms underlying BC progression, and opening avenues for targeted therapeutic approaches.

PD-1 expression on T-cells might serve as an adverse biomarker for lymphoma patients undergoing autologous stem cell transplantation, however further validation by larger prospective studies is required.

In vivo, the combination therapy induced more proliferative KLRG1-high PD1-low CD8+ T-cells and activated CD103+ DC in the tumor site and increased tumor-specific CD44+ CD8+ T-cells in the lymph node. Overall, the combination therapy of C-REV with 2'3'-cGAMP elicited antitumor immune memory responses and significantly enhanced systemic antitumor immunity in both treated and non-treated distal tumors.

Moreover, highly proliferative CD8 T cells in the B group had less PD-1 expression than those highly proliferative CD8 T cells in the DC group. The findings of this study suggest that B and DC could generate distinctive CD8 T cells, which potentially serve multiple purposes in cellular vaccine development.

Re-exposing the ex vivo-activated CD8+ T cells to tumor by adoptive transferring them to CT2A tumor-bearing mice revealed that BVax elicited immunological memory and potentiated GzmB+ production of CD8+ T cells. This study suggests that BVax and DC have distinctive interactions with CD8+ T cells, with the former poise CD8+ T cells at a more stem-like state, allowing them to differentiate upon tumor encounter.

We present novel metrics of HER2 heterogeneity via HDmIF, which offer detailed characterization of the diversity of HER2 expression in a large, clinically-annotated cohort with long-term follow-up. Identification of a strong association between immunophenotype and RFS supports further investigation of the highly immune activated subsets of ER-/HER2+ breast cancer. Strong correspondence of HER2 IF and IHC and our HAIQu methodology offers a pathway to translation of HER2het metrics to clinical practice.

To further demonstrate the role of PD-L1, we treated the PDL1-high expression cells MDA-MB-231, PD-L1 silenced MDA-MB-231 clones, and PD-L1 low expression cells MCF-7 with Durvalumab, an anti-PD-L1...Here, we further characterized the cellular autonomic role of PD-L1 in breast cancer and showed a differential role of basal PD-L1 expression in PD-L1 checkpoint inhibitors treatment efficacy. This suggests a potential role in monitoring PD-L1 expression indirect biomarkers (i.e. miR-320a, miR-145 and CD73) during ICIs treatment.

Immune-associated transcriptomic features, particularly CD8+ T cells were associated with pCR response to ICI in dMMR CRC. Heterogeneity of TME within dMMR CRC may help to discriminate patients with complete response to neoadjuvant ICI.

PDL1 is a latent prognostic factor in stage III BC and is closely related to some clinicopathological features. PDL1 expression in tumor tissues is significantly associated with better lifetime rate in stage III BC.

Results The multi-site blinded analysis across a cohort of 188 IO-treated patients (treated with nivolumab, pembrolizumab, atezolizumab or durvalumab) demonstrated the intra- and inter-tumoral heterogeneity of the PD-1/PD-L1 immune checkpoint engagement and notably showed no correlation between the extent of PD-1/PD-L1 interaction and PD-L1 expression (rs=0. This would both capture patients excluded from checkpoint immunotherapy (high PD-1/PD-L1 interaction but low PD-L1 expression, 24% of patients), and additionally avoid the treatment of patients resistant to this type of treatment (low PD-1/PDL1 interaction but high PD-L1 expression) who may benefit from alternative cancer therapeutics, such as other immunotherapies. Even at this early stage, QF-Pro® has set an unbiased quantitative cut-off to be considered for anti-PD-1/PD-L1 therapies which can be deployed directly into clinical practice.

In this study, we have demonstrated that the genes associated with immune checkpoint genes can be utilized as a prognostic biomarker for HCC. Notably, PD-1 gene expression in PBMCs has a great potential for estimating survival outcomes of patients with HCC.

The prognosis of UCEC patients with PD1 overexpression phenotype is worse than that of the PD1 low group, which is due to the involvement of the PD1 gene in the T-cell receptor signaling pathway. This study provides a further theoretical basis and reference for targeted therapy against PD1.

TILs are a heterogenous group of immune cells that recognize and attack the tumor, thus are utilized in various clinical trials. In our study, we explored the TILs in patients with kidney cancer by expanding the TILs using a clinical-grade protocol, as well as observed their characteristics and ability to recognize the tumor using in-depth experimental and computational tools.

Introduction: KRAS is the most common oncogenic driver of non-small cell lung cancer, and in the past year, 2 agents, sotorasib and adagrasib, have been approved by the FDA for treatment of advanced KRAS G12C NSCLC. We identified 61 patients with KRAS G12C NSCLC over seven years. 14.7% of patients were Black, and among patients with stage IV disease, 13.5% were Black. Black and White patients were similar in age and smoking status, and prior work from our group shows no difference in medical comorbidities.

In conclusion, patients who underwent allo-SCT exhibited high PD-1 expression, suggesting that allo-SCT increases PD-1 expression on T cells, and the patients with high PD-1 expression on CD8+T cells after allo-SCT showed the poor prognosis. For these patients, PD-1 blockade could be an immunotherapeutic strategy.

Dual-luciferase assays indicated that miR-139-5p interacted with the 3' untranslated region (3'-UTR) of PD1. These results showed that paeonol alleviates PD1-mediated antitumor immunity by reducing miR-139-5p expression and demonstrated a novel mechanism for melanoma immunotherapy.

A low-baseline PD1+ peripheral granulocyte percentage is associated with responses to atezolizumab-bevacizumab treatment in advanced HCC. These findings encourage evaluating this minimally invasive, cheap, and easy test in further independent cohorts and outlining the relevance of innate immunity in the response to immune-checkpoint inhibitors.

However, In vivo LLC1 murine lung cancer syngeneic model showed highest attenuated tumor growth when vTRAIL was treated (WT < vAng1 < vTRAN < vTRAIL), which was in accordance with CD8 high PD1 low expression levels in the tissues. It concludes that engineered vaccinia virus harboring TRAIL (vTRAIL) is the promising therapeutic option for in vivo lung cancer therapy.

Dual chemotherapy (i.e., Pemetrexed and Cisplatin, CT) plus anti-VEGF Bevacizumab could be associated with anti-PD1 such as Pembrolizumab in NSCLC patients with low PDL1 levels. The Beva followed by low dose Pemetrexed + Cisplatin group is thus the more likely to harness tumor immunity, with peaks in CD4+ and CD8+ T cells and drop in Tregs observed on D14. This pilot study suggests therefore that sequencing Beva + CT low dose followed by a two-week lag time prior to administrating anti-PD1 could lead to synergism in lung cancer models.

Overall survival was predicted with CA19-9 and PDL1 levels (p = 0.0074, p = 0.23, respectively). PDL1 and CA19-9 may act as a probable predictor of a poor prognosis in gallbladder cancer (GBC) cases.

TP53 mutations could represent a potential biomarker for treatment selection for pts with low PDL1 expression treated with chemo-immunotherapy. Prospective validation is needed.

The results showed that the high TCTS scoring group showed dismal prognosis, improved sensitivity to oxaliplatin and good response to anti-PD-1/PD-L1 immunotherapy. Moreover, the low TCTS score group had few genomic alterations, low immune activation and low PD-1/PD-L1 expression levels. In conclusion, TCTS is an ideal biomarker for predicting the clinical outcomes and improving precision treatment of HCC.

Initial MDTB recommendations including definitive chemo-RT with subsequent consolidation durvalumab were not ideal due large primary tumor and low performance status. Extrapolating from other tumor types’ outcome data may not translate as optimistically to NSCLC. Further review of population-based data on dMMR/MSI-H NSCLC and SMARCA-4UT is warranted to elucidate outcomes of PD-1 inhibitor treatment on these tumor types

The TME in DLBCL is important and cases that lack both checkpoint inhibitors PD1 and TIM3 in the TME have a poor OS and PFS. Decreased expression of these markers was associated with loss of HLA class I protein expression on the surface of the tumor cells, which allows these cells to evade immune surveillance.

"Prevalence of dMMR/MSI-H and TMB-H is very low in HCC. PD-L1 is only expressed in <20%. Even with a finding of strong association of expression of several established IO biomarkers with PD-L1 expression, it’s still not predictive of response to ICI."

In BAL from advanced LC patients, T cells present features of exhaustion. T cells in t-BAL could be the best surrogate of tumor-infiltrating T cell, and future studies should evaluate T cell phenotype and density as potential biomarkers for cancer immunotherapy outcome.

There is a generalized blunting of immune response in EMVI positive colorectal carcinoma, which may contribute to a worse prognosis. Tumor-associated macrophages seem to play the most significant role in determining EMVI.

10% had Afatinib, 50% for Gefitinib, 27% for Erlotinib, & 13% for Osimertinib. However, PD-L1 status had no significant correlation with TKI treatment. Further research are needed to establish consistency in the observed findings.

2013-246 and RGS0000003289) in compliance with the Declaration of Helsinki. Consent All participants signed a consent form which is saved at ECU research database.

Conclusions High CTLA4 or GITR in the context of low PDL1 may represent an intermediate-T cell-inflamed TME and/or tumor cell-intrinsic expression. Stratification of tumors by T cell-inflamed gene signature, or PDL1 status, as well as expression of a specific therapeutic target may identify patient populations who could benefit from CTLA4 or GITR depletion strategies in IO combination therapies.

No abstract available

The PD-1/PD-L1 may induce immune suppression in OLK and accelerate the progress of malignant transformation.

Conclusions Here we report that high PDL1 NSCLC are associated with distinct pre-treatment TCR repertoire and HLA-I supertypes comparing to low PDL1. Mechanistic studies are required to understand the biology of different types of NSCLC and hence have positive influence on treatment personalisation.

A human mAb, canakinumab, targeting the proinflammatory cytokine IL-1β, significantly decreased the risk of lung cancer in the Canakinumab Anti-inflammatory Thrombosis Outcomes Study...In querying the TCGA dataset, we interestingly found positive correlations between IL1B expression and infiltration of immunosuppressive polymorphonuclear cells and expression of their chemoattractant, CXCL1, and PDCD1 expressions in patients with KM-LUAD. Our data provide evidence that IL-1β blockade may serve as a preventive strategy among high-risk individuals and an alternative therapeutic approach in combination with currently available treatments for KM-LUAD.

Four patients with repeated episodes of eruptive KA-like and lichenoid lesions developing 2-7 months after commencing pembrolizumab for AJCC stage IV melanoma, were recruited. The patients best responded to acitretin and were managed surgically if they demonstrated neoplastic features. Accelerated squamoproliferative growth in actinically damaged keratinocytes associated with lichenoid eruptions may be unmasked in patients treated with anti-PD1 immunotherapy potentially contributed to by a local cutaneous immunosuppressed TME.

The signature constructed by pairing irlncRNAs and frlncRNAs showed a notable clinical predictive value.

Pathway enrichment showed that the focal adhesion (P=0.005) and actin cytoskeleton (P=0.022) pathways were associated with OS. This study aimed to identify the classification of hot and cold tumors, and develop a novel signature to predict the ICI treatments response for PD-1/PD-L1 high expression NSCLC patients.

Furthermore, an immune risk score model was established based on multivariate Cox regression, and the risk score was determined to be an independent prognostic factor for NSCLC patients. These results indicate that the immune context is heterogeneous because of the complex interactions of different components and that using multiple factors in combination might be promising for predicting the prognosis of and stratifying NSCLC patients.

P2, N=24, Recruiting, Ever Supreme Bio Technology Co., Ltd. | Trial completion date: Jun 2022 --> Dec 2023 | Trial primary completion date: Dec 2021 --> Dec 2022

In HCC, nivolumab and pembrolizumab are described as possible second line therapies. In concordance with previous reports, we found an association between low frequency of PD-1 expression and increased HCC recurrence, as well as the lack of impact of PD-L1 expression on HCC recurrence. Furthermore, our results suggest that HCC recurrence may be more frequent in immune-exclusive tumors. Pembrolizumab as adjuvant instead of 2nd line therapy should be further investigated.

The Kaplan-Meier analysis suggested that high ARID1A expression combined with low PD-L1 expression or low PD1+ TIL counts is associated with the best prognosis in patients with GBC. ARID1A inactivation can lead to a worse prognosis in patients with GBC, potentially by mediating immune evasion through the PD1/PD-L1 pathway.