Modeling the tumor–immune interface with translational relevance remains one of the biggest hurdles in oncology research. Organotypic tumor slice cultures (OTSCs) are gaining traction as a powerful bridge between clinical relevance and experimental control. These
ex vivo platforms preserve tumor architecture, vasculature, and immune cell composition allowing researchers to probe the interactions between tumor and immune compartments in ways that more closely mimic
in vivo biology. In
OncoImmunology (
Sivakumar, et al., 2019), researchers develop OTSCs into a robust, medium-throughput model for functional drug and immunotherapy testing. By combining syngeneic mouse tumor models and patient-derived xenograft (PDX) tumors, they demonstrate that OTSCs offer a versatile tool for translational immune-oncology research.
A Platform that Preserves the Tumor–Immune Interface
Traditional preclinical models often fail to recapitulate the immunosuppressive microenvironments seen in human tumors. Animal models lack human immune complexity, while organoids typically exclude immune cells altogether. OTSCs overcome these limitations by maintaining endogenous immune cell populations, including tumor-infiltrating CD45
+ leukocytes, within intact tumor slices. Sivakumar et al. developed a complete pipeline for tissue slicing, culturing, and analysis using live imaging, flow cytometry, and cytokine profiling. Their model enables both intrinsic tumor analysis and functional testing of immune-modulatory drugs such as checkpoint inhibitors and bispecific antibodies. Crucially, the OTSC system supports tumor tissue from both treatment-naïve and previously treated patients, allowing researchers to compare therapy responses across disease states.
Comparative Models, Multiplexed Readouts
Using OTSCs from multiple murine and human tumors, the team found CD45⁺ leukocyte infiltration ranging from 5–60%. They then detected the subsequent differential cell types and normalized results using CD45
+ levels to show that frequencies of immune populations were similar between the primary tumor and the OTSC models
- CD4+ and CD8+ tumor-infiltrating lymphocytes (TILs)
- Tumor-associated macrophages (TAMs)
- Tumor-associated neutrophils (TANs)
- Natural killer (NK) cells
- Tumor-associated dendritic cells (TADCs)
- Tumor-infiltrating B cells (B TILs)
- Tumor-associated monocytes (TAMonocytes)
Functional assays were then used to compare response of OTSCs to both organoid cultures and PDX tumors against cytotoxic and targeted agents including vandetanib, dabrafenib, teniposide, and topotecan. These experiments included both untreated controls and slices treated with isotype control antibodies. For these immunotherapy-focused assays, the following Bio X Cell antibodies were employed:
Results showed that drug responses in OTSCs generally aligned with matched organoid and PDX models, confirming OTSCs as a viable and dynamic model system for evaluating tumor–immune interactions in a cross-species and near-native context.
Translational Relevance and Antibody Performance
This work affirms the value of
ex vivo systems that preserve immune complexity while enabling experimental control. OTSCs offer a unique platform for interrogating immune-modulatory strategies, particularly when precise antibody performance is critical. Bio X Cell’s
InVivoMAb and InVivoPlus antibodies are well-suited to these models, offering validated
in vivo performance, stringent endotoxin screening, and formulations optimized for translational research. With antibodies available for both human and mouse targets, Bio X Cell supports researchers aiming to explore immune checkpoint biology, therapeutic resistance, and tumor–immune co-evolution across species and systems.
