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Updated: Jul 29, 2025
Visualization, Quantification, and Mapping of Immune Cell Populations in the Tumor Microenvironment
Published on: March 25, 2020
Deciphering the tumour immune microenvironment cell by cell
M Nabhan1, D Egan1, M Kreileder1
1Systems Biology Ireland, School of Medicine, University College Dublin, Belfield, Ireland.
Abstract:
Immune checkpoint inhibitors (ICIs) have rejuvenated therapeutic approaches in oncology. Although responses tend to be durable, response rates vary in many cancer types. Thus, the identification and validation of predictive biomarkers is a key clinical priority, the answer to which is likely to lie in the tumour microenvironment (TME). A wealth of data demonstrates the huge impact of the TME on ICI response and resistance. However, these data also reveal the complexity of the TME composition including the spatiotemporal interactions between different cell types and their dynamic changes in response to ICIs. Here, we briefly review some of the modalities that sculpt the TME, in particular the metabolic milieu, hypoxia and the role of cancer-associated fibroblasts. We then discuss recent approaches to dissect the TME with a focus on single-cell RNA sequencing, spatial transcriptomics and spatial proteomics. We also discuss some of the clinically relevant findings these multi-modal analyses have yielded.
Insights
Immune checkpoint inhibitors (ICIs) show promise in cancer therapy, but variable response rates highlight the need for biomarkers. The tumor microenvironment (TME) significantly impacts ICI efficacy and resistance.
Area of Science:
- Oncology
- Immunology
- Cancer Biology
Background:
- Immune checkpoint inhibitors (ICIs) have transformed cancer treatment, offering durable responses in some patients.
- However, response rates to ICIs vary significantly across different cancer types, necessitating the identification of predictive biomarkers.
- The tumor microenvironment (TME) plays a critical role in mediating both response and resistance to ICIs.
Purpose of the Study:
- To review the modalities that shape the TME, including metabolic factors, hypoxia, and cancer-associated fibroblasts.
- To discuss advanced techniques for dissecting TME complexity, such as single-cell RNA sequencing, spatial transcriptomics, and spatial proteomics.
- To highlight clinically relevant findings derived from multi-modal TME analyses.
Main Methods:
- Review of existing literature on TME composition and its influence on ICI therapy.
- Focus on single-cell RNA sequencing (scRNA-seq) for cellular heterogeneity.
- Integration of spatial transcriptomics and proteomics for spatial context.
Main Results:
- The TME is a complex ecosystem with dynamic cell-cell interactions and environmental influences (metabolism, hypoxia, fibroblasts).
- Multi-modal analyses provide unprecedented resolution into TME composition and its impact on ICI outcomes.
- These advanced techniques are yielding clinically relevant insights into ICI response and resistance mechanisms.
Conclusions:
- Understanding the TME is crucial for improving ICI therapy efficacy.
- Advanced single-cell and spatial technologies are powerful tools for dissecting TME complexity.
- Biomarkers derived from TME analysis hold promise for predicting and enhancing patient response to ICIs.
Related Concept Videos
02:17The Tumor Microenvironment
01:27Tumor Immunotherapy