Product Citations: 34

The 4662 KPC model is one of the most widely used mouse models of pancreatic cancer. It represents an excluded immune phenotype and closely recapitulates the pathophysiology of pancreatic cancer in humans. We set out to identify the endogenous neoepitopes present in 4662 cells. By combining whole-exome and RNA-sequencing and a bioinformatic neoantigen prediction pipeline, we have identified 15 potential candidate neoantigen epitopes. Ten more highly expressed were selected for validation in an in vivo vaccination study with 4662-tumor bearing mice. The Mrps35-derived neoantigen was found to be immunogenic as we have identified endogenous T-cells responding to this neoepitope, and the response was significantly increased upon vaccination with a synthetic peptide and upon PD1-IL2v therapy. Dextramers based on this peptide were validated and can be used to monitor endogenous tumor-specific CD8+ T-cells in response to immunotherapy. This will support the development of novel therapies for this highly unmet medical need indication.

  • Cancer Research
  • Immunology and Microbiology

Deep metabolic profiling of immune cells by spectral flow cytometry-A comprehensive validation approach.

In IScience on 18 July 2025 by Wishart, C. L., Spiteri, A. G., et al.

The advancing field of immunometabolism requires tools that link single-cell metabolism with immune function. Metabolic flow cytometry provides this capability, but its broad adoption has been limited by costly custom reagents and a lack of standardized methods for validating metabolic targets. Here, we present a standardized and user-friendly spectral flow cytometry panel that profiles eight key metabolic pathways at single-cell resolution using only commercially available antibodies, enabling simultaneous analysis of immune phenotype and metabolic activity . Applying this approach to lung myeloid and T cells following intranasal adenoviral CD40L vaccination revealed distinct metabolic phenotypes between resident and infiltrating myeloid cells, as well as functionally divergent metabolic programs in naive, effector, and tissue-resident memory T cells. Additionally, leveraging NAD(P)H autofluorescence allowed label-free detection of glycolysis and expanded the panel's utility. This standardized approach reduces cost and experimental complexity, enabling researchers to elucidate how metabolism drives immune function across broader immunological and clinical contexts.
© 2025 The Author(s).

  • Biochemistry and Molecular biology
  • Cell Biology
  • Immunology and Microbiology

RORγt inverse agonists demonstrating a margin between inhibition of IL-17A and thymocyte apoptosis.

In PLoS ONE on 17 January 2025 by Collins, M., Pehrson, R., et al.

Multiple genetic associations suggest a causative relationship between Th17-related genes coding for proteins, such as IL-17A, IL-23 and STAT3, and psoriasis. Further support for this link comes from the findings that neutralizing antibodies directed against IL-17A, IL-17RA and IL-23 are efficacious in diseases like psoriasis, psoriatic arthritis and ankylosing spondylitis. RORγt is a centrally positioned transcription factor driving Th17 polarization and cytokine secretion and modulation of RORγt may thus provide additional benefit to patients. However, RORγt also plays a role in the normal development of T cells in the thymus and genetic disruption of RORγt in the mouse leads to the development of lymphoma originating in the thymus. Whilst it is not established that down-regulation of RORγt activity would lead to the same consequence in humans, further understanding of the thymus effects is desirable to support progress of this target as a potential treatment of Th17-driven disease. Herein we present the characterisation of recently disclosed RORγt inverse agonists demonstrating target engagement and efficacy in vitro and in vivo against Th17 endpoints but requiring higher concentrations in vitro to affect thymocyte apoptosis.
Copyright: © 2025 Collins et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

  • FC/FACS
  • Mus musculus (House mouse)

Tumor stage-driven disruption of NK cell maturation in human and murine tumors.

In IScience on 15 November 2024 by Russick, J., Torset, C., et al.

Natural killer (NK) cells play a pivotal role against cancer, both by direct killing of malignant cells and by promoting adaptive immune response though cytokine and chemokine secretion. In the lung tumor microenvironment (TME), NK cells are scarce and dysfunctional. By conducting single-cell transcriptomic analysis of lung tumors, and exploring pseudotime, we uncovered that the intratumoral maturation trajectory of NK cells is disrupted in a tumor stage-dependent manner, ultimately resulting in the selective exclusion of the cytotoxic subset. Using functional assays, we observed intratumoral NK cell death and a reduction in cytotoxic capacities depending on the tumor stage. Finally, our analyses of human public dataset on lung cancer corroborate these findings, revealing a parallel dysfunctional maturation process of NK cells during tumor progression. These results highlight additional mechanisms by which tumor cells escape from NK cell cytotoxicity, therefore paving the way for tailored therapeutic strategies.
© 2024 The Author(s).

  • Cancer Research

Anti-PTHrP blockade limits CD8+ T-cell exhaustion in anti-cancer immunotherapy

Preprint on BioRxiv : the Preprint Server for Biology on 28 October 2024 by Moes, B., Gao, Y., et al.

Cancer is a major global health concern, with immune suppression hindering treatment. Immunotherapy, specifically immune checkpoint blockage on T cells, has revolutionized cancer treatment. T-cell exhaustion is an abnormal activation state that develops when continuous exposure to antigens, like cancer. In this context, recent evidence suggests that parathyroid hormone-related protein (PTHrP) plays a previously underappreciated role in fostering an immunosuppressive tumor microenvironment. Further, blocking PTHrP activity reduces primary tumor growth, prevents metastasis, and prolongs survival in mice with various cancers. Here, we confirm that administration of anti-PTHrP monoclonal antibodies can reduce the growth of B16-PDL1 melanoma tumors and that although the therapy did not alter the presence of CD4+ and CD8+ TILs, we noted that all stages of T-cell exhaustion were reduced. Further, the expression of cytolytic proteins PERFORIN and GZMB also increased. By contrast, anti-PTHrP therapy increased the relative presence of pre-pro B cells with a decline in mature B cells in the bone marrow. Overall, our data indicates that anti-PTHrP therapy acts by reducing T-cell exhaustion and by affecting B-cell development. These provide further mechanistic evidence to support the application of anti-PTHrP blockade as an alternate therapeutic approach to boost anti-tumor immunity.

  • Mus musculus (House mouse)
  • Cancer Research
  • Immunology and Microbiology
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