A live tumor fragment platform to assess immunotherapy response in core needle biopsies while addressing challenges of tumor heterogeneity

作者：T. S. Ramasubramanian, Pichet Adstamongkonkul, Christina M. Scribano, Christin Johnson, Sean Caenepeel, Laura Hrycyniak, Lindsey Vedder, Nicholas Dana, Christian Baltes, Victoria L. Browning, Yuan-I Chen, Thomas Dietz, Evan Flietner, Nicholas Kaplewski, Anna Kellner, Michael Korrer, Chao Liu, Nathan Marhefke, Payton McDonnell, Amreen Nasreen, Victoria Pope, Abhijeet Prasad, Jordyn Richardson, Sidney Schneider, Mikaela Schultz, Chetan Sood, Aishwarya Sunil, Erika von Euw, Eric Wait, Ellen E. Wargowski, Pooja Advani, Barbara Broome, Antje Bruckbauer, Andrew K. Godwin, Nima Kokabi, Yanyan Lou, Robert C. G. Martin, Mercedes Robaina, Giuseppe Vincenzo Toia, Joshua Routh, Andreas Friedl, Kevin W. Eliceiri, Michael Szulczewski, Scott Johnson, Jon Oliner, Jérôme Galon, Christian M. Capitini, Debabrata Mukhopadhyay, Janis Taube, David Braun, Hinco J. Gierman · 发表于：Journal of Translational Medicine · 年份：2026 · DOI：10.1186/s12967-025-07378-2 · 被引用次数：2 · 研究领域：Cancer Immunotherapy and Biomarkers、Cancer Cells and Metastasis、Immunotherapy and Immune Responses

BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, providing durable and even curative responses. However, most patients do not respond and current biomarkers (eg, programmed death 1 ligand 1 [PD-L1]), mismatch repair deficiency [dMMR]/high microsatellite instability [MSI] and tumor mutational burden) lack predictive accuracy. Ex vivo profiling of patient-derived tumor fragments shows promise as a predictive biomarker but relies on substantial surgical tissue to mitigate intra-specimen heterogeneity. Innovations are needed that address these challenges, particularly where limited tissue is available such as in core needle biopsies (CNBs). METHODS: Live tumor fragments (LTFs) were generated from 59 human tumor resections and 31 CNBs from patients enrolled in observational clinical trials (ClinicalTrials.gov identifiers: NCT05478538, NCT05520099, NCT06349642) to assess cytokine induction following ICI treatment. LTFs were encapsulated in hydrogel and cultured ex vivo for up to 72 hours. A sequential treatment strategy that applies control and treatment within the same well was used with response to ICI or αCD3/αCD28 assessed using a multiplex secretome assay. Viability was assessed using established metabolic assays and dynamic optical coherence microscopy. RESULTS: LTFs maintained viability and retained T cells responsive to stimulation throughout ex vivo culture. Multiplex immunofluorescence and immunohistochemistry showed key components of ...