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Updated: Nov 5, 2025

Predictive Immune Modeling of Solid Tumors
Published on: February 25, 2020
Single-cell Analysis Technologies for Immuno-oncology Research: from Mechanistic Delineation to Biomarker Discovery
Zhiliang Bai1, Graham Su2, Rong Fan3
1Department of Biomedical Engineering, Yale University, New Haven, CT 06511, USA; State Key Laboratory of Precision Measurement Technology and Instrument, Tianjin University, Tianjin 300072, China.
Abstract:
The successes with immune checkpoint blockade (ICB) and chimeric antigen receptor (CAR)-T-cell therapy in treating multiple cancer types have established immunotherapy as a powerful curative option for patients with advanced cancers. Unfortunately, many patients do not derive benefit or long-term responses, highlighting a pressing need to perform complete investigation of the underlying mechanisms and the immunotherapy-induced tumor regression or rejection. In recent years, a large number of single-cell technologies have leveraged advances in characterizing immune system, profiling tumor microenvironment, and identifying cellular heterogeneity, which establish the foundations for lifting the veil on the comprehensive crosstalk between cancer and immune system during immunotherapies. In this review, we introduce the applications of the most widely used single-cell technologies in furthering our understanding of immunotherapies in terms of underlying mechanisms and their association with therapeutic outcomes. We also discuss how single-cell analyses help to deliver new insights into biomarker discovery to predict patient response rate, monitor acquired resistance, and support prophylactic strategy development for toxicity management. Finally, we provide an overview of applying cutting-edge single-cell spatial-omics to point out the heterogeneity of tumor-immune interactions at higher level that can ultimately guide to the rational design of next-generation immunotherapies.
Insights
Single-cell technologies enhance understanding of cancer immunotherapy. These methods reveal mechanisms, predict patient responses, and guide development of next-generation cancer treatments.
Area of Science:
- Immunology
- Oncology
- Biotechnology
Background:
- Cancer immunotherapies like immune checkpoint blockade (ICB) and chimeric antigen receptor (CAR)-T-cell therapy show promise but lack efficacy in many patients.
- Understanding the complex interactions within the tumor microenvironment is crucial for improving treatment outcomes.
Purpose of the Study:
- To review the application of single-cell technologies in unraveling cancer immunotherapy mechanisms.
- To highlight how single-cell analyses aid in biomarker discovery, resistance monitoring, and toxicity management.
- To discuss the potential of single-cell spatial-omics for designing future immunotherapies.
Main Methods:
- Review of current literature on single-cell technologies (e.g., single-cell RNA sequencing, single-cell ATAC sequencing).
- Analysis of how these technologies characterize immune cells and tumor heterogeneity.
- Exploration of spatial-omics for understanding tumor-immune interactions.
Main Results:
- Single-cell technologies provide deep insights into immune cell function and tumor microenvironment composition.
- These methods facilitate the identification of predictive biomarkers for immunotherapy response.
- Single-cell analyses are instrumental in understanding mechanisms of resistance and developing strategies to overcome it.
Conclusions:
- Single-cell technologies are revolutionizing cancer immunotherapy research by elucidating complex biological processes.
- Future applications, including spatial-omics, will enable more precise and effective immunotherapy design.
- Advancements in single-cell analysis promise to improve patient outcomes and expand the utility of cancer immunotherapies.

