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  • Multi-omic landscape of human gliomas from diagnosis to treatment and recurrence. Cancer cell Piyadasa, H., Oberlton, B., Ribi, M., Leow, K., Ranek, J. S., Averbukh, I., Amouzgar, M., Liu, C. C., Franchina, D. G., Greenwald, N. F., McCaffrey, E. F., Kumar, R., Ferrian, S., Tsai, A. G., Filiz, F., Fullaway, C. C., Bosse, M., Varra, S. R., Kong, A., Sowers, C., Gephart, M. H., Nuñez-Perez, P., Yang, E., Travers, M., Schachter, M. J., Liang, S., Santi, M. R., Bucktrout, S., Gherardini, P. F., Connolly, J., Cole, K., Barish, M. E., Brown, C. E., Oldridge, D. A., Drake, R. R., Phillips, J. J., Okada, H., Prins, R., Bendall, S. C., Angelo, M. 2025

    Abstract

    Gliomas are among the most lethal cancers, with limited treatment options. To uncover hallmarks of therapeutic escape and tumor microenvironment (TME) landscape, we applied spatial proteomics, transcriptomics, and glycomics to 670 lesions from 310 adult and pediatric patients. Single-cell analysis shows high B7H3+ tumor cell prevalence in glioblastoma (GBM) and pleomorphic xanthoastrocytoma, while most gliomas, including pediatric cases, express targetable tumor antigens in less than 50% of tumor cells, potentially explaining trial failures. Paired samples of isocitrate dehydrogenase (IDH)-mutant gliomas reveal recurrence driven by tumor-immune spatial reorganization, shifting from T cell and vasculature-associated myeloid cell-enriched niches to microglia and CD206+ macrophage-dominated tumors. Multi-omic integration identified N-glycosylation as the best classifier of grade, while the immune transcriptome best predicted GBM survival. Provided as a community resource, this study offers a framework for glioma targeting, classification, outcome prediction, and a baseline of TME composition across all stages.

    View details for DOI 10.1016/j.ccell.2025.11.006

    View details for PubMedID 41386224

  • Multi-omic landscape of human gliomas from diagnosis to treatment and recurrence. bioRxiv : the preprint server for biology Piyadasa, H., Oberlton, B., Ribi, M., Ranek, J. S., Averbukh, I., Leow, K., Amouzgar, M., Liu, C. C., Greenwald, N. F., McCaffrey, E. F., Kumar, R., Ferrian, S., Tsai, A. G., Filiz, F., Fullaway, C. C., Bosse, M., Varra, S. R., Kong, A., Sowers, C., Gephart, M. H., Nuñez-Perez, P., Yang, E., Travers, M., Schachter, M. J., Liang, S., Santi, M. R., Bucktrout, S., Gherardini, P. F., Cole, K., Barish, M. E., Brown, C. E., Oldridge, D. A., Drake, R. R., Phillips, J. J., Okada, H., Prins, R., Bendall, S. C., Angelo, M. 2025

    Abstract

    Gliomas are among the most lethal cancers, with limited treatment options. To uncover hallmarks of therapeutic escape and tumor microenvironment (TME) evolution, we applied spatial proteomics, transcriptomics, and glycomics to 670 lesions from 310 adult and pediatric patients. Single-cell analysis shows high B7H3+ tumor cell prevalence in glioblastoma (GBM) and pleomorphic xanthoastrocytoma (PXA), while most gliomas, including pediatric cases, express targetable tumor antigens in less than 50% of tumor cells, potentially explaining trial failures. Longitudinal samples of isocitrate dehydrogenase (IDH)-mutant gliomas reveal recurrence driven by tumor-immune spatial reorganization, shifting from T-cell and vasculature-associated myeloid cell-enriched niches to microglia and CD206+ macrophage-dominated tumors. Multi-omic integration identified N-glycosylation as the best classifier of grade, while the immune transcriptome best predicted GBM survival. Provided as a community resource, this study opens new avenues for glioma targeting, classification, outcome prediction, and a baseline of TME composition across all stages.

    View details for DOI 10.1101/2025.03.12.642624

    View details for PubMedID 40161803

    View details for PubMedCentralID PMC11952471

  • Chemical generation of checkpoint inhibitory T cell engagers for the treatment of cancer. Nature chemistry Szijj, P. A., Gray, M. A., Ribi, M. K., Bahou, C., Nogueira, J. C., Bertozzi, C. R., Chudasama, V. 2023

    Abstract

    Bispecific T cell engagers (BiTEs), a subset of bispecific antibodies (bsAbs), can promote a targeted cancer cell's death by bringing it close to a cytotoxic T cell. Checkpoint inhibitory T cell engagers (CiTEs) comprise a BiTE core with an added immunomodulatory protein, which serves to reverse cancer-cell immune-dampening strategies, improving efficacy. So far, protein engineering has been the main approach to generate bsAbs and CiTEs, but improved chemical methods for their generation have recently been developed. Homogeneous fragment-based bsAbs constructed from fragment antigen-binding regions (Fabs) can be generated using click chemistry. Here we describe a chemical method to generate biotin-functionalized three-protein conjugates, which include two CiTE molecules, one containing an anti-PD-1 Fab and the other containing an immunomodulatory enzyme, Salmonella typhimurium sialidase. The CiTEs' efficacy was shown to be superior to that of the simpler BiTE scaffold, with the sialidase-containing CiTE inducing substantially enhanced T cell-mediated cytotoxicity in vitro. The chemical method described here, more generally, enables the generation of multi-protein constructs with further biological applications.

    View details for DOI 10.1038/s41557-023-01280-4

    View details for PubMedID 37488375

    View details for PubMedCentralID 6182456

  • ANTIBODY-LECTIN BISPECIFICS FOR GLYCO-IMMUNE CHECKPOINT BLOCKADE Stark, J., Gray, M., Wisnovsky, S., Ibarlucea-Benitez, I., Riley, N., Ribi, M., Ravetch, J., Bertozzi, C. BMJ PUBLISHING GROUP. 2022: A1254

    View details for DOI 10.1136/jitc-2022-SITC2022.1209

    View details for Web of Science ID 000919423401318

https://orcid.org/0000-0001-6816-8326