Biology subjects

IJsselsteijn, M. E.

Publications and source records attributed to IJsselsteijn, M. E..

3 recordsLinked to original sources

bioRxiv2025

Divergent Therapeutic and Prognostic Impacts of Immunogenic Features in Undifferentiated Soft Tissue Sarcoma and Myxofibrosarcoma

Myxofibrosarcoma and undifferentiated soft tissue sarcoma (USTS) are genetically complex soft tissue sarcomas with distinct morphological features. Treatment typically involves surgery, often combined with neoadjuvant chemo- or radiotherapy. To better understand the immunobiology of these sarcomas and its associations with treatment response and prognosis, we performed transcriptomic and immunophenotypic profiling. RNA sequencing was performed on 13 USTS and 10 myxofibrosarcomas and immunological profiles were compared with soft tissue sarcoma data from The Cancer Genome Atlas (n = 206 including 44 USTS and 17 myxofibrosarcomas). Immune contextures were further evaluated in 16 USTS and 11 myxofibrosarcomas using imaging mass cytometry. Characterization of T cell and macrophage infiltration in tumors was further assessed in 23 USTS and 22 myxofibrosarcomas through multispectral immunofluorescence and immunohistochemical analysis. USTS and myxofibrosarcomas demonstrated immunogenic features compared to other soft tissue sarcomas, with subsets of USTS and myxofibrosarcomas demonstrating high T cell infiltration while USTS demonstrated a higher infiltration by myeloid cells as compared to myxofibrosarcoma. Prognostically, T cells and CD68+CD163+ macrophages were associated with metastasis-free survival in USTS but not in myxofibrosarcomas. Notably, in USTS, neoadjuvant radiotherapy appeared to induce cytotoxic T cell infiltration and depletion of myeloid cells, whereas these effects were not observed in myxofibrosarcomas. These findings highlight important differences in the immunobiology of USTS and myxofibrosarcomas with therapeutic and prognostic implications. These differences should be taken into account given the growing availability of immunotherapeutic options for treating patients with soft tissue sarcomas.

cancer biology↗

bioRxiv2025

NK cell-macrophage interactions in granulomas correlate with limited tuberculosis pathology

Development of novel vaccines and treatment approaches against tuberculosis are hampered by limited knowledge of what constitutes a protective immune response against Mycobacterium tuberculosis (Mtb). Granulomas are organized immune aggregates that form in the lung in response to mycobacterial infection and are an important site of pathogen-host interaction. The composition and cellular microenvironment within the granuloma impacts the bacterial control capacity. To identify protective responses in granulomas, imaging mass cytometry was used to study archived lung tissue from low dose Mtb-infected non-human primates presenting with various levels of disease. This approach revealed that granuloma composition is correlated with the severity of lung pathology. Granulomas of animals with limited lung pathology were enriched for NK cells showing increased interactions with tissue macrophages. This work improves our understanding of local immune interactions in the lung and how these correlate with severity of tuberculosis disease. Author summaryTuberculosis remains the deadliest infectious disease in the world with 10 million new infections and 1.5 million deaths annually. The existing vaccine is not effective enough to halt the tuberculosis epidemic. In order to develop an improved vaccine, more complete and detailed knowledge on the immune responses that can successfully protect against tuberculosis is required. Individuals that are exposed to Mycobacterium tuberculosis, the pathogen that causes tuberculosis disease, fall along a spectrum, with some individuals showing a strong innate capacity to protect against disease, while others fall ill. By studying these differences in a model organism, namely non-human primates, we can learn about protective immune responses. In primates with limited disease, the immune cell aggregates surrounding the bacteria in the lung contained more NK cells than were found in severe disease. In addition, interactions between NK cells and macrophages, cells that can eat bacteria, were seen a lot more in protected animals. This suggests that the interaction between NK cell and macrophages contributes to controlling tuberculosis disease, this knowledge can contribute to improved vaccine strategies.

immunology↗

bioRxiv2021

Iron-loading is a prominent feature of activated microglia in Alzheimer's disease patients

Brain iron accumulation has been found to accelerate disease progression in Amyloid {beta}-positive Alzheimer patients, though the mechanism is still unknown. Microglia have been identified as key-players in the disease pathogenesis, and are highly reactive cells responding to aberrations such as increased iron levels. Therefore, using histological methods, multispectral immunofluorescence and an automated in-house developed microglia segmentation and analysis pipeline, we studied the occurrence of iron-accumulating microglia and the effect on its activation state in human Alzheimer brains. We identified a subset of microglia with increased expression of the iron storage protein ferritin light chain (FTL), together with increased Iba1 expression, decreased TMEM119 and P2RY12 expression. This activated microglia subset represented iron-accumulating microglia and appeared morphologically dystrophic. Multispectral immunofluorescence allowed for spatial analysis of FTL+Iba1+-microglia, which were found to be the predominant A{beta}-plaque infiltrating microglia. Finally, an increase of FTL+Iba1+-microglia was seen in patients with high Amyloid-{beta} load and Tau load. These findings suggest iron to be taken up by microglia and to influence the functional phenotype of these cells, especially in conjunction with A{beta}.

neuroscience↗