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Gene & Protein in Disease Insights from In situ spatial profiling

biomarkers may appear in a small cohort of patients or 6. Single-cell spatial profiling delves into
samples, for clinical application, they must be validated the TME
in a larger group of samples, tens to hundreds or even
more patients. The seamless integration from discovery The TME – a dynamic ecosystem of malignant cells,
to clinical applications ensures consistent and reliable immune infiltrates, stromal components, and extracellular
results across various research phases, providing a unique matrix – functions as both a protective shield and a growth
advantage in workflow scalability. accelerator for tumors. By fostering immunosuppression
and nutrient-rich niches, the TME enables tumors to evade
Spatial profiling brings together not only the “what” immune detection, resist therapy, and drive metastatic
or the “who,” but also the crucial “where,” adding critical spread or dormancy. This intricate interplay positions the
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spatial context. This is significant because, in immuno- TME as a critical determinant of therapeutic outcomes,
oncology, biomarkers are often not just a “yes” or “no” making its characterization essential for designing next-
answer – such as cell density or the presence of different generation immunotherapies that dismantle tumor
cell types or proteins – but also include information on defenses.
how these elements are interconnected.
Immunotherapies – including checkpoint inhibitors
In this regard, the NanoString GeoMx Digital Spatial and targeted blockade therapies – leverage the body’s
Profiling technology has demonstrated strong analytical immune defenses to target cancer; however, their efficacy
performance, with validation supported by both regression remains limited to a minority of patients. Emerging
analysis and clinical outcome correlation. Leveraging spatial profiling technologies, which map the expression
its high-plex capabilities, this platform has enabled the of immune and cancer cell biomarkers within the
identification of multiple expression signatures linked TME, are now illuminating mechanisms of treatment
to patient outcomes – most notably, the association resistance. By revealing intricate cellular interactions
between programmed death-ligand 1 expression in tumor- and spatial heterogeneity, these tools are revolutionizing
associated macrophages and therapeutic response. 19 our understanding of the TME, offering actionable
5. Advances in single-cell multiomics for insights to enhance patient stratification and optimize
cancer immunotherapy immunotherapy design. This progress holds promise for
expanding therapeutic responsiveness and delivering
Every human being is composed of approximately 30 precision immunotherapies to a broader range of patient
trillion cells. The functionality of each cell – and, populations.
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by extension, the human body – relies on physical, Single-cell spatial profiling platforms enable
signaling, and microenvironmental interactions with comprehensive mapping of tumor biopsies, producing
neighboring cells. Single-cell multiomics (SCMO) aims detailed spatial phenotypic signatures that guide
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to understand these complex interactions by integrating precision treatment selection. Researchers are leveraging
various biomolecular hierarchies, such as the genome, this technology to dissect differences in the TME between
transcriptome, and epigenome. For instance, SCMO patients who respond to therapies and those who develop
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has shown that the profile of immune cells in the TME resistance. In immunotherapy, the TME has emerged as a
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can be crucial in determining clinical outcomes. critical predictor of disease progression and therapeutic
SCMO is increasingly recognized as a valuable tool in outcomes. Distinct spatial profiles – capturing tumor and
cancer immunotherapy and other medical applications. stromal features, such as cellular density, transcriptional
Continuous SCMO-related benchwork and computational activity, and tissue architecture – enable clinicians
tool development are essential for enhancing its utility in to forecast treatment efficacy using spatially resolved
cancer immunotherapy. 24 biomarkers. The growing ability to decode these
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Chimeric antigen receptor (CAR) T-cell immunotherapy spatially informed molecular patterns is unraveling
utilizes a patient’s genetically modified immune cells to the TME’s complexities, from immune evasion
target cancer. Despite being the focus of hundreds of mechanisms to stromal interactions. As this field
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clinical trials, CAR T-cell therapy carries a significant advances, the integration of spatial profiling into clinical
risk of short-term relapse and severe side effects. SCMO practice holds transformative potential, offering novel
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could potentially enhance the efficacy and safety of CAR strategies to overcome therapy resistance and improve
T-cell therapy. 27,28 cancer care.

Volume 4 Issue 3 (2025) 6 doi: 10.36922/GPD025050007