PD-1 overexpression

By synergizing the ICD effect of Cur and the PD1/PDL1 axis blocking function of genetically engineered NVs, the PD1@Cur-PLGA enhanced the intratumoral infiltration rate of mature dendritic cells and CD8+ T cells in tumor tissues, resulting in significantly inhibiting tumor growth in breast and prostate tumor-bearing mouse models. This synergistic ICD and ICB therapy based on genetically engineered NVs provides a low-cost, safe, and effective strategy to enhance cancer immunotherapy.

These findings indicate that elevated PD-1 expression on TILs can be associated with immune evasion during the early stages of malignancy evolution in the NSCLC setting and further research is required to further delineate the role of PD-1/PD-L1 pathway on tumor immune senescence. These results underline the potential role of PD-1/PD-L1 inhibitors in the treatment of early-stage NSCLC.

Malignant transformation of NF1-PNST is characterized by an immunosuppressive microenvironment comprising of TAM with high expression of PD-L1, which are associated with inferior outcomes. These findings suggest a clinical potential of immune modulating therapeutics that can unleash an anti-tumor immune response.

This permits improved control of chronic infection without additional immunopathology. Together, these results demonstrate that tuning PD-1 via epigenetic editing can reduce CD8+ T cell dysfunction while avoiding excess immunopathology.

In addition, we found that the frequency of cytotoxic ILCs and NKp46+ILC3 in tumors positively correlates with monocytic cells and conventional type 2 dendritic cells, revealing potentially new interconnected immune cell subsets in the tumor microenvironment. Consequently, these observations may have direct relevance to tumor microenvironment composition and how ILC subset may influence anti-tumor immunity.

Our data show that the depletion of circulating MAIT cells is a common observation in a broad spectrum of haematological malignancies. In addition to their reduced numbers, MAIT cells acquire an activated/exhausted phenotype.

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 conclusion, IL-32 potentially induced by inflammatory conditions and anticancer therapy and contribute to immune escape of cancer cells via development the immunosuppressive microenvironment. IL-32 might be a target molecule for anti-cancer therapy.

Our strategy employed pH-responsive carriers, poly(ethylene glycol)-poly(β-amino esters) amphiphilic block copolymer (PEG-PAEs), for delivering apatinib (an angiogenesis inhibitor), that were surface-coated with plasma membrane derived from engineered cells overexpressing PD-1 proteins (an immune checkpoint inhibitor to block PD-L1)...Importantly, our nanomedicine selectively accumulated in both small and large HCC occupying >50% of the liver volume to exert therapeutic effects with minimal systemic side effects. Overall, these findings highlight the potential of such multifunctional nanoconverters to effectively reshape the tumor microenvironment for advanced HCC treatment.

However, we found no advantage for anti-PD-1 against PD-1 high expressing Vδ2 T cells in promoting pyroptosis. Taken together, our work demonstrated that Vδ2 T cells combined with anti-PD-1 antibody can be developed as a potential combination immunotherapy for mesothelioma.

In this study, a prognostic transcriptomic-based signature of 14 genes has been defined and validated for PDAC. This signature clearly identifies two prognostic groups that could constitute the basis for tailored immunotherapy with specific IC inhibitors. LAG-3 is a promising target for immunotherapy in PDAC patients.

The analysis of the data collected in this paper highlights several key parameters with prognostic value and statistical significance: the EBV infection at diagnosis, its association with low-intensity BCL2(+), the presence of CD68 with rosette formation, and the identification of specific vascularization patterns. The development of prognostic systems that take into account the integration of biological prognostic markers seems essential for a better risk stratification.

Our group showed a selective response (~40%) with the PD-1 blocking antibody pembrolizumab in patients with RT, particularly after prior exposure to ibrutinib (Ding et al, Blood, 2017)...SHP-1 (TPI-1) and SHP-1+SHP-2 (TPI-1+TNO155) inhibitor treatment promoted OCI-LY19 cell death and led to recovery of phosphorylation on ATM, Chk-2 and p53 in these cells... Our data showed robust PD-1 expression in patients with Richter transformation from CLL to DLBCL. PD-1 overexpression in DLBCL lymphoma cell lines enhanced cell proliferation in vitro and in vivo. Further investigation identified that PD-1 modified the phosphorylation/function of SHP phosphatases and thereby regulated p53 pathways (Figure 1).

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.

Multiple immunofluorescence staining confirmed the overexpression of Kindlin-3 in the glioma-associated microglia/macrophages (GAMs). The findings of this study provide a new perspective on the role of Kindlin-3 in glioma and may have a significant impact on the discovery of novel biomarkers and targeting of GAMs in the future.

Moreover, we find that blocking the specific receptor (PD-1) using antibodies significantly relieves the S. aureus-imposed inhibition. Our findings suggest that therapeutically targeting PD-1 is a possible future strategy for treating certain antibiotic-resistant staphylococcal infections.

Unfortunately, the well-known cuproptosis initiator, disulfiram and copper complex (DSF/Cu), also increases PD-L1 level in tumors, which may diminish the final therapeutic outcome...After CuX-P treatment with laser irradiation, strong anti-tumor immune responses are stimulated in a mouse model with triple-negative breast cancer. Thus, this study develops a tumor-targeted biomimetic system that offers simultaneous cuproptosis killing, photothermal therapy (PTT) and immunotherapy in mice.

In this study, we report the PD-1 expression as a tool for differential diagnosis between SS and other etiologies, including MF, and between early stages of MF and BID. Also, it was noted that the detection high expression of PDL-1 correlates with an unfavorable form of the disease. That is, in all cases of SS, a comparable high expression of both PD-1 and PDL-1 was noted, which also affects the aggressive course of the disease.

In summary, we develop a simple, effective, safe and widely-applicable biological membrane modification strategy. This "subtractive" strategy displays some advantages and is worth further development.

Our observations consolidated the clinicopathological and molecular characteristics of uterine MLA. Both clinicians and pathologists should consider these features to make an accurate diagnosis of uterine MLA and to ensure appropriate therapeutic management of this rare entity.

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.

In the case of Lu-DOTA-PD-L1-i, the radiation dose delivered to the lung micrometastases was ten times (43 mGy/MBq) that delivered to the kidneys (4.20 mGy/MBq) and fifty times that delivered to the liver (0.85 mGy/MBq). Therefore, the radiotherapeutic PD-L1-i ligands of Ac and Lu developed in this research could be combined with immunotherapy to enhance the therapeutic effect in various types of cancer.

This gentleman’s complex medical background included; multisystemic IgG4 related disease involving the liver, lung and oesophagus requiring; oseophagectomy and gastric transposition; and medical management with Azathioprine and Prednisolone. Due to role of PD-1, would Cemiplimab6 have been an option for treatment in this patient with IgG4 malignancy?

Conclusions Our study shows for the first time how obesity, through the Ob-R/leptin axis, might activate TILs. However, this was not translated into higher CR; probably due to high PD-1 expression as exhaustion feature.

We demonstrate that obesity is associated with lung carcinogenesis in both clinical cohorts as well as preclinical models, refuting the concept of an obesity paradox for lung carcinogenesis. This phenomenon is associated with Treg and CD8+ T cell exhaustion related immunosuppression in the lung. This finding highlights the importance of addressing obesity in patients at risk for lung cancer.

The inhibitory effect of GPD1 on breast cancer cells was also weakened after treatment with LY294002, a PI3K/AKT pathway inhibitor...Meanwhile, we detected that the relationship between GPD1 level and survival rate presents a positive correlation in breast cancer patients from the Cancer Genome Atlas (TCGA) database. Therefore, GPD1 can be a prognostic biomarker and target in developing therapeutic strategies for breast cancer patients.

tropicalis) can promote CRC tumor growth and chemotherapy resistance to oxaliplatin by regulating mismatch repair system...tropicalis can down-regulate tumor cell-intrinsic PD-1 expression via enhancing tumor cells autophagy levels to promote CRC progression. It may provide a new idea and mechanism for answering why the immune monoclonal antibody treatment is ineffective in cancer patients.

The combination treatment of Abrine and anti-PD-1 antibody has a synergistic effect on suppressing the tumor growth through up-regulating CD4 or CD8 T cells, down-regulating the Foxp3 Treg cells, and inhibiting the expression of IDO1, CD47, and PD-L1. Overall, this study reveals that Abrine as an IDO1 inhibitor has an inhibition effect on immune escape and has a synergistic effect with the anti-PD-1 antibody on the treatment of HCC.

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.

FACS analysis of xenograft tumors revealed an increased percentage of tumor infiltrating T-cells. We identified a set of CDX and PDX models without interference with parallel injection of PBMC, T- or NK-cell preparations for the evaluation of immune cell engagers and other cell therapies.ConclusionWe established human tumor-immune-cell models of different entities using CDX or PDX in combination with different donor derived immune cell subsets as effector cells.These models allow preclinical, translational studies on tumor immune biology as well as evaluation of new therapies, drug combinations and biomarker identification and validation.

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In conclusion, our deep learning-based BLEACH&STAIN framework facilitates rapid and comprehensive assessment of more than 60 spatially orchestrated immune cell subpopulations and its prognostic relevance. Implications: The development of an easy-to-use high-throughput 15+1 multiplex fluorescence approach facilitates the in-depth understanding of the immune tumor microenvironment and enables to study the prognostic relevance of more than 130 immune cell subpopulations.

Our findings indicate the possible mechanisms by which anti-PD-1 agents may contribute to the treatment of MDS. These insights may provide mutation-specific treatment as a supplementary therapy for MDS patients with high-risk mutations, such as TP53, N-RAS or other complex mutations.

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.

We further loaded P-NVs with 2-deoxy-D-glucose (2-DG) and doxorubicin (DOX), and found that these drugs co-loaded P-NVs efficiently shrank lung cancers in mouse models for both allograft and autochthonous tumor. 2-DG loaded nanoparticles thus activate anti-tumor activities of T cells in the tumor microenvironment. Our work thus highlights the promising antitumor activity of PDG-NVs, which warrants further clinical evaluation.

Finally, we evaluated the functionality of the model by the treatment with checkpoint inhibitors like Ipilimumab (Ipi), Nivolumab (Nivo) or Pembrolizumab (Pembro). Treatment with Ipi, Nivo or Pembro led to a minor tumor growth delay. Response to checkpoint inhibitors showed a correlation to innate immune response and PD-L1 expression of PDX and could further be increased by combination with radiotherapy.ConclusionsOur humanized immune-PDX models enable appropriate preclinical translational research on tumor immune biology and the evaluation of new therapies and combinations, as well as the identification and validation of biomarkers for immune therapy, especially in rare PDX models.

Conclusion Our results suggest that loss of HSPDI in the context TNBC cells may promotes oncogenic transformation to an intermediary luminal progenitor phenotype that gains differentiation plasticity based on the upregulation of Estrogen-receptors signaling pathways. Ongoing analyses will be performed to identify the possible links between loss of HSPD1 and key transcription factors that define mammary epithelial cell differentiation.

In conclusion, YIV-906 modulates adaptive immunity by activating T effector cells mainly through its action on SHP1/2. YIV-906 could also facilitate immune checkpoint blockade therapy or CAR-T cell therapy for cancer treatment.

This multidisciplinary clinical study decodes for the first time how obesity, through the OB-R/leptin axis, might activate TILs but apparently dysfunctional as it is not translated into higher pCR; probably due to the presence of exhausted features such as high PD-1 expression. The role of Ob-R together with PD-1 as a potential biomarker for immunotherapy should be further explored.

We also found evidence of resistance via PD1 overexpression in responders. Implications: Finally, we identified candidates drugs to reverse AA/P resistance : topoisomerase inhibitors and drugs targeting the cell cycle via the MYC/AURKA/AURKB/TOP2A and/or PI3K/AKT1/MTOR pathways.

In summary, the iPDX models reproduced key features of the corresponding human tumor. The observed variability and high PD-1 expression are important considerations that need to be addressed in order to develop a reproducible model system.