In what ways is spatial biology contributing to the development of personalized medicine approaches, particularly in oncology?

In the run-up to the American Spatial Biology Congress, we are asking speakers to share their thoughts about the developments that are taking place in this rapidly developing field.

In the first of these mini blogs we asked Yi Liu, Ph.D., M.Med Assistant Professor of Biomedical Informatics, Mayo Clinic College of Medicine and Science Bioinformatician, Dept. of Quantitative Health Sciences (QHS) Mayo Clinic Spatial Biology Core “In what ways is spatial biology contributing to the development of personalized medicine approaches, particularly in oncology?”

This is what she had to say.

Spatial biology, as demonstrated in my research on triple-negative breast cancer (TNBC), plays a pivotal role in advancing personalized medicine, especially in oncology. By analyzing cellular behavior and interactions within the native tissue microenvironment, spatial biology offers insights that go beyond traditional bulk or single-cell transcriptomics. Here’s how spatial biology contributes to personalized medicine, particularly in TNBC and other cancers.

Understanding Tumor Heterogeneity: TNBC is characterized by significant intratumoral heterogeneity, which complicates treatment strategies. Spatial biology enables the examination of cellular composition, gene expression, and protein abundance at single-cell resolution within the tumor and its microenvironment. This detailed mapping helps identify unique tumor subpopulations and their spatial arrangement, which may drive treatment resistance or metastatic potential. For example, differences in the spatial distribution of immune cells like T CD8 and Tregs between responders and non-responders to immunotherapy can guide patient stratification.

Deciphering Tumor-Immune Interactions: Spatial biology allows clinicians to pinpoint immune-enriched regions and understand how immune cells respond to therapy. This data can help refine immunotherapy regimens, such as checkpoint inhibitors, by targeting patients with a favorable immune microenvironment or modifying treatment to enhance immune cell infiltration in “cold” tumors.

Biomarker Discovery: Spatially resolved biomarkers provide more accurate predictors of therapy response compared to bulk measures. Biomarkers such as HLA-DRA or IFNα expression can be used to tailor treatments to patients most likely to benefit, enhancing efficacy while minimizing unnecessary toxicity.

Mechanistic Insights into Resistance: Understanding the spatial dynamics of resistance mechanisms allows for the development of combination therapies. For example, treatments that enhance MHC expression or promote T cell infiltration into resistant regions may improve outcomes for TNBC patients.

Advancing Spatial Transcriptomics and Imaging: The CosMx platform enables high-resolution spatial transcriptomics, identifying millions of cells and mapping their spatial relationships. This provides unparalleled insight into the functional and spatial context of each cell. The ability to analyze spatial gene expression at single-cell resolution supports the design of more precise interventions. In TNBC, spatial analysis helps identify immune hotspots or immune-excluded regions, guiding local delivery of therapies such as cytokines or immune-boosting agents.

Application to Neoadjuvant and Adjuvant Therapy: Neoadjuvant pembrolizumab-based chemotherapy benefits from the evaluation of early immune responses, as demonstrated by my study’s findings on T cell activation and interferon pathways. Spatial profiling of pre-treatment biopsies can identify patients likely to respond to specific therapies. Post-treatment spatial analysis can help monitor residual disease or early markers of recurrence, enabling timely intervention.

Spatial biology is redefining oncology by unraveling the intricate interactions within the tumor microenvironment. Its application in TNBC exemplifies how spatially resolved data can transform our understanding of cancer biology and enable personalized, more effective treatments tailored to the unique molecular and spatial characteristics of each patient.

Yi Liu is a speaker at the American Spatial Biology Congress.

Join her and 30 other speakers in San Diego.