scResponse: A Rank-Based Method for Identifying Cell States That Contribute to Immunotherapy Response by Single-Cell
Qi Dong1,2, Haijun Huang3, Yuxiu Wang3
1Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, China.
Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|March 23, 2026
Summary
A new algorithm, scResponse, quantifies single-cell responses to immunotherapy, revealing how cellular states impact treatment efficacy. This tool aids in discovering new strategies to improve immunotherapy effectiveness in cancer patients.
Area of Science:
- Cancer Research
- Immunology
- Computational Biology
Background:
- Immunotherapy shows promise in cancer treatment but often lacks long-term efficacy.
- Understanding cellular diversity is key to improving treatment outcomes.
- Current methods for evaluating immunotherapy efficacy at single-cell resolution are limited.
Purpose of the Study:
- To develop an efficient algorithm, scResponse, for quantifying single-cell responses to immunotherapy.
- To link therapeutic response to specific single-cell states and biological processes.
- To identify novel targets for enhancing immunotherapy sensitization.
Main Methods:
- Development and application of the scResponse algorithm.
- Analysis of single-cell sequencing data to capture cellular subtype and state influences.
- Integrated analysis across multiple cancer types to identify metabolic pathway associations.
Main Results:
- scResponse quantifies single-cell responses, revealing influences of vascular normalization, macrophage polarization, CD8+ T cell exhaustion, and fibroblast subtypes.
- Key metabolic pathways linked to immunotherapy response: glyoxylate/dicarboxylate metabolism (sensitizing) and retinol metabolism (suppressing).
- Validation of opposing roles of glyoxylate and retinol metabolism in co-culture and mouse models.
Conclusions:
- scResponse is an effective tool for mapping immunotherapy efficacy to single-cell states.
- The algorithm enables mechanistic insights into divergent therapeutic outcomes.
- Findings facilitate target discovery for novel immunotherapy sensitization strategies.
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