From nanoparticles to niche reprogramming: spatial transcriptomics reveals therapy-responsive microenvironments

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Uyar R., Ceylan A., Yılmazer Aktuna A.

EMBL Conference: Spatial biology: the melting pot, Heidelberg, Almanya, 14 - 17 Ekim 2025, ss.251, (Özet Bildiri)

  • Yayın Türü: Bildiri / Özet Bildiri
  • Basıldığı Şehir: Heidelberg
  • Basıldığı Ülke: Almanya
  • Sayfa Sayıları: ss.251
  • Ankara Üniversitesi Adresli: Evet

Özet

212

From nanoparticles to niche reprogramming: spatial transcriptomics

reveals therapy-responsive microenvironments

Recep Uyar1, Ahmet Ceylan1, Sanjiv Dhingra2, Acelya Yilmazer1

1 Ankara University, Turkey

2 University of Manitoba, Canada

Presenter: Recep Uyar

The spatial distribution of nanoparticles within tumors may not only influence drug

penetration but also reprogram the tumor microenvironment (TME) in a region-specific

manner. Here, we integrate spatial transcriptomics with immune phenotyping to dissect how

varying intratumoral levels of MXene quantum dot (MQD) accumulation—classified as High,

Normal, Low, and Naive (untreated)—modulate local immune architecture and functional

potential.

We performed systematic immune signature scoring for each region of interest (ROI),

calculating metrics including T cell inflammation (TIS) score, interferon-gamma (IFN-γ)

signatures, immune exclusion/desert markers, macrophage M1/M2 polarization ratios, and

tertiary lymphoid structure (TLS) activity. Importantly, we also included B cell and

neutrophil-specific transcriptional signatures as part of the spatial scoring framework,

enabling a more comprehensive mapping of innate and adaptive immune cell activity across

MQD-defined regions. Additionally, we adapted TIDE-like models to predict localized

immunotherapy responsiveness based on spatial transcriptional cues.

Preliminary findings indicate that MQD-rich regions exhibit increased expression of

immune-activating signals and enhanced B cell and neutrophil-associated gene programs.

These features, however, display spatial variability and suggest context-dependent immune

reprogramming that could inform region-specific therapeutic strategies.

By combining spatially resolved gene expression with quantitative immune scoring and

predictive modeling, this study highlights how nanoparticles may generate immunologically

responsive niches within tumors. This approach offers a translational framework for

understanding the spatial mechanics of nanotherapeutic function and for identifying

candidate zones for spatially guided immunotherapy.