Biology subjects

van de Sande, M. A. J.

Publications and source records attributed to van de Sande, M. A. J..

3 recordsLinked to original sources

bioRxiv2026

Cheating (re)shapes pathogen virulence and antifungal resistance

Filamentous fungi grow as fused, multinucleate networks that share secreted public goods vs private goods. We asked whether this sharing enables "cheater" nuclei to increase in frequency by exploiting goods produced by other nuclei, and whether such social conflict shapes virulence and antifungal resistance. We tested this in the gray mold pathogen Botrytis cinerea by contrasting an extracellular detoxification trait, a public good (enzymatic hydrolysis of the tomato saponin alpha-tomatine) with an intracellular antibiotic resistance trait, a private good (hygromycin phosphotransferase). In pairwise competitions, tomatinase-deficient nuclei gained advantage when rare against a constitutive producer, both in vitro and in planta, even though producers drive lesion expansion. An ordinary differential equation model fitted to the competition outcomes identified antibiotic gradients as the key driver of frequency-dependent selection and predicted stable coexistence of producer and non-producer nuclei across multinucleate bottlenecks. Cheating within fungal syncytia can therefore decouple virulence from reproduction and buffer the selection on antifungal resistance.

genetics↗

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↗

bioRxiv2022

Interactions in CSF1-driven Tenosynovial Giant Cell Tumors

The majority of cells in Tenosynovial Giant Cell Tumor (TGCT) are macrophages responding to CSF1 that is overproduced by a small number of neoplastic cells with a chromosomal translocation involving the CSF1 gene. Treatment with inhibitors of the CSF1 pathway has been clinically effective. An autocrine loop was postulated where the neoplastic cells are stimulated through the CSF1 receptor (CSF1R) expressed on their surface. Here we show that the neoplastic cells themselves do not express CSF1R and therefore may be unaffected by current therapies. We identified a new marker for synoviocytes, GFPT2, that highlights the tumor cells in TCGT and is associated with activation of the YAP1/TAZ pathway. The neoplastic cells in TGCT are highly similar non-neoplastic synoviocytes. Finally, we provide molecular support for the osteoclast-like features of the giant cells in TGCT that correlate with the destructive effects of TGCT on bone.

cancer biology↗