Overcoming Drug Resistance in Pediatric Cancers: From CAR-T Failure to Tumor Microenvironment Reprogramming

Recent advances in CAR-T cell therapy, single-cell and spatial multi-omics technologies, and translational immunology have revealed previously unrecognized mechanisms of immune escape, treatment-induced cellular reprogramming, and TME-mediated therapeutic resistance in pediatric tumors.

This Special Topic aims to bring together cutting-edge basic, translational, and clinical studies addressing the evolving landscape of drug resistance in pediatric cancers, with particular emphasis on immunotherapy resistance, TME remodeling, developmental mechanisms, and next-generation therapeutic strategies.

Topics of interest include, but are not limited to:

1. CAR-T cell failure, antigen escape, and immune exhaustion in pediatric malignancies;

2. Tumor microenvironment-mediated resistance in pediatric solid tumors and brain tumors;

3. Stem-like cell populations, minimal residual disease, and treatment-induced quiescence;

4. Epigenetic and metabolic reprogramming associated with therapeutic resistance;

5. Spatial and single-cell approaches for decoding resistant pediatric tumors;

6. Developmental and age-specific mechanisms influencing treatment response;

7. Novel immunotherapies, bispecific antibodies, antibody-drug conjugates, and rational combination strategies;

8. Translational and early-phase clinical studies addressing resistance mechanisms and therapeutic vulnerabilities in pediatric and adolescent/young adult (AYA) cancers.

Through this collection, we hope to foster interdisciplinary collaboration across pediatric oncology, immunology, developmental biology, and translational medicine, ultimately accelerating the development of resistance-informed therapeutic strategies for children and adolescents with cancer.