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Updated: Jan 17, 2026
Tractable In Vivo Reprogramming of Tumor Cells to Type 1 Conventional Dendritic Cell-like Cells
Published on: August 1, 2025
Rationalized combinatorial targeting of immune co-receptors leads to tumor regression
Saleha Nisar1, Prashant Chauhan2, Ashok Patidar2
1Department of Zoology, Savitribai Phule Pune University, Pune 411007, Maharashtra, India; National Centre for Cell Science, Ganeshkhind, Pune 411007, Maharashtra, India.
Abstract:
Different co-stimulatory and co-inhibitory molecules influence the dynamicity of an immune response. As their expression levels may collectively decide the amplitude and quality of an anti-tumor immune response, we proposed that the expression of these molecules would be dynamically modulated during a progressive tumor growth and that the study of their expression levels would guide fixing a combinatorial target for anti-tumor immunotherapy. Based on the kinetics of expression of 33 immune molecules within the tumor and draining lymph nodes during RM-1-induced progressive prostate tumor model in C57BL/6 mice, a three-phase combinatorial anti-tumor immunotherapy was designed. Phase- specific treatments with combinations of blocking antibodies against co-inhibitory receptors and agonistic antibodies against stimulatory receptors resulted in significant tumor regression and cytokines' expression, suggesting a strategic personalized anti-tumor immunotherapy with enhanced therapeutic efficacy, reduced toxicity and the risk of treatment failures.
Insights
This study reveals that dynamic immune molecule expression during tumor growth guides personalized anti-tumor immunotherapy. Combining blocking and activating antibodies effectively reduced tumors and boosted immune responses.
Area of Science:
- Immunology
- Cancer Research
- Immunotherapy
Background:
- Co-stimulatory and co-inhibitory molecules critically regulate immune responses.
- Their expression dynamics are crucial for determining the effectiveness of anti-tumor immunity.
- Understanding these dynamics can inform novel combinatorial immunotherapy strategies.
Purpose of the Study:
- To investigate the dynamic modulation of immune molecule expression during progressive tumor growth.
- To identify combinatorial immunotherapy targets based on these expression kinetics.
- To design a phase-specific immunotherapy for enhanced anti-tumor effects.
Main Methods:
- Studied the expression kinetics of 33 immune molecules in tumor and draining lymph nodes.
- Utilized a C57BL/6 mouse model with RM-1 prostate tumor.
- Developed a three-phase combinatorial immunotherapy strategy using blocking and agonistic antibodies.
Main Results:
- Demonstrated dynamic changes in immune molecule expression correlating with tumor progression.
- Phase-specific immunotherapy treatments led to significant tumor regression.
- Observed enhanced cytokine expression following combinatorial treatments.
Conclusions:
- Dynamic immune molecule profiling can guide personalized anti-tumor immunotherapy.
- A phase-specific combinatorial approach offers enhanced therapeutic efficacy.
- This strategy may reduce toxicity and treatment failure risks in cancer immunotherapy.
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