PD-1 expression

SH2B2 appears to act as an oncogene in COAD and may serve as a pivotal prognostic and therapeutic target, deserving further exploration.

Using bemcentinib, a selective AXL inhibitor, we observed reduced binding affinity in the PD-1/AXL interaction, although it was not abrogated...Also, the interacting residues remain conserved in both species, indicating an important biological function of the interaction. Our study shed light on the molecular basis of the PD-1/AXL interaction with the implication for its conservation across species, providing a foundation for future research aimed at improving immunotherapy strategies and developing novel therapeutic approaches.

Drug sensitivity analysis suggested that Metformin, Gefitinib, and Lapatinib may be more effective in the low-risk group, while Pyrimethamine, Axitinib, and Rapamycin may be more beneficial for high-risk patients. In summary, we identified a 6-gene signature related to dendritic cell dysfunction that can predict prognosis in esophageal cancer, offering valuable insights for personalized therapeutic strategies.

Instead, deletion of TOX impaired the effector function of T cells in chronic sepsis, contradicting its impact on short-term TCR engagement. Our study provides a novel insight into sepsis-induced T-cell exhaustion, highlighting the distinct characteristics of T-cell exhaustion programmed by sepsis.

P2, N=9, Completed, Mayo Clinic | Active, not recruiting --> Completed | Trial completion date: Oct 2025 --> Oct 2024

The integrative analysis provides new insights into molecular complexities of BRCA. Immune profiles and gene signatures hold potential for improving stratification of BRCA patients and guiding the development of personalized immunotherapy strategies.

These gated CAR-T cells exhibited lower expression of exhaustion markers (PD1, Tim3, LAG3, and CD39), higher frequency of memory T cells (CD62L+CD45RA+), and enhanced expansion. While targeting AML, the moderated circuit CAR signal also helped to mitigate cytokine release syndrome, potentially addressing one of the ongoing challenges in CAR-T immunotherapy.

This study identified three biomarkers and constructed a diagnostic model, providing a new perspective for the research and treatment of GC.

All in all, our results highlight NK cells and innate CD8 T-cells harboring cytotoxic content, as well as global downregulation of PD-1-expression on effector T-cells, as potential predictive functional signatures for successful TFR in CML. Considering innate CD8 T-cells, further investigations are needed to determine whether their possible contributory role in cancer surveillance in CML could be extended to other cancers, and also whether their targeting by immune cheek-point inhibitors could enhance their anti-tumoral functions.

However, during NCP BVDV infection, a synergistic effect of PD-1 blockade and AA led to the inhibition of viral replication and the promotion of IFN-γ production. Our findings provided new insights into the immunopathological mechanisms of BVDV and the potential value of anti-viral strategies based on AA treatment alone or in combination with PD-1 blockade.

Further investigation revealed that RTP-W reversed the exhaustion of CD8+ T cells by reducing PD-1 expression and promoting cell proliferation and cytokine expression, primarily through the activation of the Akt signaling pathway. These findings indicate that RTP-W has promising potential as an immunomodulatory agent with antitumor effects.

DAC treatment increased immunogenicity and decreased proliferation in HNSCC cells while enhancing expression of co-stimulatory ICM GITR and OX40. We propose low dose DAC treatment as a adjuvant to immunotherapy.

All patients underwent surgery followed by temozolomide concurrent with and adjuvant to radiotherapy...The expression of PD-L1 in GBM IDH-wt patients is confined to a small subpopulation. While we found a significant association between low CD4+ lymphocyte density (≤10%) and survival, given the small numbers of our cohort, the prognostic value of CD4+ lymphocyte density will need to be validated in large-scale studies.

Our study identified a cluster of genes in ovarian cells that are suppressed by obesity, including those belonging to HSP family genes. These findings provide valuable insights for investigating the link between obesity and ovarian diseases.

P2, N=50, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting

The higher expression of PD-1 and PD-L1 may contribute to tumor progression. Therefore, combinational immunotherapy by these immune checkpoint inhibitors might be a promising strategy for clinical improvement in patients with thyroid cancer, especially those with ATC.

TFL regulates the expression of miR-146a to inhibit the PD-1/PD-L1 signaling pathway in THP-1 cells, regulates the immune barrier of sepsis induced in cell inflammation model in vitro, and thus protects LPS induced THP-1 cells.

These findings indicate that TCR-transduced CD8 T cells can undergo antigen-dependent expansion when exposed to TriVax. Additionally, the expression of CA-STAT5 enhances T cell proliferation and persistence, partly by promoting resistance to PD-1/PD-L1-mediated inhibition in antitumor T cells.

Mechanistically, HCC-derived exosomal miR-500a-3p directly influences SOCS2 to regulate the JAK3/STAT5A/STAT5B signaling pathway. MiR-500a-3p promotes the growth and migration of HCC through the SOCS2/JAK3/STAT5A/STAT5B axis.

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.

Although our findings suggested a link between extracellular miRNAs and immunosuppressive biomarkers, this association did not achieve validation in the external cohort, possibly due to population heterogeneity. Collectively, this study advanced our understanding of the epigenetic orchestration of health hazards of Cr(VI) by exosomal miRNAs, shedding light on their expression signatures and their intricate interplay with Cr(VI)-induced genetic and immunological perturbations, thus providing novel perspectives on the toxic pathways of heavy metals.

The aptamer was converted into a fluorescent probe and its potential in molecular imaging was demonstrated in a culture of human cells overexpressing PD1 and murine pancreatic organoids / immune cells mixed co-culture model. We conclude that the provided aptamers are suitable probes for imaging of PD1 expressing immune cells even in complex cellular models and may find future utility as diagnostic tools.

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.

NOG (NOD/Shi- scid /IL-2R null ) and NOG-EXL (huGM-CSF/huIL-3 NOG) mice conditioned with Busulfan underwent i.v. injection of human CD34+ cells...In this context, animal models that recapitulate human disease are greatly needed. Leveraging xenograft tumors derived from patients with advanced HCCs and a commercially available immunodeficient mouse strain that expresses human GM-CSF and IL-3, we demonstrate a novel but accessible approach for modeling the HCC tumor microenvironment.

In vitro we have shown that the addition of TGF-β1 antibody or CD38 antibody can effectively inhibit the proportion of CD38high Tregs. This study describes the characteristics of DHMM based on bicentric data, which is helpful to better provide theoretical support for the treatment of DHMM.

Considering all these data, we can conclude that the expression of immunoregulatory genes depends on tumor phenotype and has potential clinical implications in BC patients.

HER2 and other tumor-associated antigens have served as valuable benchmarks for developing novel therapies, such as antibody engagers and CAR T-cells. However, further research is essential to identify and validate new target antigens that can enhance therapeutic efficacy and broaden the clinical applicability of these approaches.

Our results uncover a novel mechanism of PD-1 regulation, and identify a pharmacologically tractable target whose inhibition suppresses PD-1 abundance and T cell dysfunction.

TCM displayed a potential enhanced anti-tumor efficacy of PD-1/PD-L1 inhibitors on six types of tumor including colon, breast, colorectal, melanoma, and bladder cancer in animals. However, due to significant heterogeneity in the included studies, caution should be exercised regarding the results. More high-quality randomized controlled animal experiments are need.

Ad5-ApoA1 activates CD8+ T cells by promoting large-scale viral replication. High levels of ApoA1 protein expression promote cholesterol efflux, inhibit CD8+ T cell depletion, and reduce inflammatory factors, ultimately leading to superior therapeutic effects on hepatocellular carcinoma.

P2, N=15, Active, not recruiting, National Cancer Institute (NCI) | N=40 --> 15 | Trial completion date: Sep 2027 --> Nov 2025 | Trial primary completion date: Sep 2027 --> Sep 2024

To sum up, our findings imply that GPD1L may impede the initiation and advancement of ESCC via modulating the PI3K/AKT signaling pathway. GPD1L is considered to be a promising therapeutic target and biomarker to diagnose and treat ESCC.

P2, N=9, Active, not recruiting, Mayo Clinic | Trial completion date: Oct 2024 --> Oct 2025 | Trial primary completion date: Oct 2024 --> Oct 2025

P=N/A, N=30, Recruiting, John Kirkwood | Not yet recruiting --> Recruiting

Meanwhile, knockdown of PLCG2 could potentiate the efficacy of ICB therapy. In summary, we have identified for the first time that PLCG2 could be considered a precise biomarker and promising therapeutic target for predicting CRC prognosis, optimizing individualized treatment, reversing CRC immune escape, and overcoming resistance to ICB therapy.

P2, N=30, Active, not recruiting, David Bond, MD | Trial completion date: Jul 2024 --> Dec 2024 | Trial primary completion date: Jul 2024 --> Dec 2024

We found that the spatial context of PD-1 and TIM-3 successfully predicted the overall survival of CRC patients independent of TNM stage. Dual targeting of PD-1 and TIM-3 in mouse tumor models inhibited tumor progression and reduced T-cell exhaustion, indicating a potential strategy for improving the clinical treatment of CRC.

TIM3, the most frequently expressed ICP on CTL, followed by CTLA4, provides alternate therapeutic targets in ATC. The co-expression of multiple immune checkpoints is of great interest for ATC since these data also open the avenue for combination therapies.

The peripheral blood immunophenotype in patients with BC is altered compared with cancer-free individuals. Understanding this dysregulated immune profile will contribute to the identification of diagnostic and prognostic indicators to guide effective immune-targeted, personalized treatments.

Our data show that immune cell distribution after systemic chemotherapy changes in peripheral blood. Interestingly, in peritoneal fluid only the inhibitory Treg population decreased and local T cells within peritoneal metastases remain unaffected. These data indicate little to no effect of systemic chemotherapy on the local immune system, supporting the need for new therapeutic options.

PDL-1/TILS and PDL-1/TC are independent prognostic factors in OSCC and PDL1-/TILS has an important role.

Moreover, high expression of CXCL13 was related to a better tumor response and more extended tumor-stable stage after PD-1 blocking therapy in IMvigor210. The study concluded that CXCL13 could be a prognostic marker and a potential immunotherapy target for OC patients, especially PD-1 checkpoint blockade.