Precision Immuno-Oncology: Harnessing Novel Drug Development, Biomarkers, and Nanoparticle-Based Therapeutic Platforms to Overcome Cancer Resistance

Precision immuno-oncology represents a paradigm shift in cancer treatment, integrating advanced molecular profiling with novel drug development and nanoparticle technologies to overcome therapeutic resistance. Recent advances emphasize dismantling the immunosuppressive tumor microenvironment (TME) through strategies like macrophage polarization via PI3Kγ inhibitors, neutralizing tumor-derived exosomes with nanobodies, and STING pathway activation to convert "cold" tumors into immunogenic "hot" tumors. Concurrently, novel biomarkers refine patient stratification and real-time response monitoring, including AI-driven spatial transcriptomics of H&E slides and circulating tumor DNA (ctDNA) dynamics. Emerging therapeutic platforms combine next-generation RAS inhibitors (e.g., pan-KRAS therapies), antibody-drug conjugates with optimized payloads, and logic-gated CAR-T cells to target cancer stem cells while sparing healthy tissue. These approaches are further amplified by cutting-edge technologies such as single-cell sequencing and nanomedicine, enabling personalized combinatorial regimens that bridge immune activation with metabolic reprogramming. By synchronously addressing drug delivery challenges, nanoparticle optimization, and tumor-immune crosstalk, precision immuno-oncology aims to achieve durable remissions even in historically refractory malignancies.

This research topic aims to overcome cancer resistance by integrating advanced biomarkers, innovative therapeutic agents and nanoparticle platforms, and next-generation therapeutic platforms. Key goals include leveraging high-resolution sequencing and identifying neoantigens, predictive biomarkers, and immune signatures that guide personalized therapies. Innovations in drug design focus on improving delivery efficiency and targeting through nanoparticle carriers, while enhancing antitumor immune cell infiltration. Therapeutic innovation centers on combinatorial strategies, such as logic-gated CAR-T cells targeting dual tumor antigens, antibody-drug conjugates (ADCs) with optimized payloads, and neoantigen vaccines tested in organoid models that mimic complex drug distribution patterns. Additionally, advancing organoid-based platforms with microfluidics and AI aims to improve preclinical immunotherapy efficacy and prediction of resistance mechanisms. These efforts seek to translate molecular insights into precision regimens that overcome resistance across diverse cancers.

We welcome the submission of Original Research, Review, Mini Review, and Perspective articles on themes including, but not limited to:
• Targeting tumor-associated macrophages, myeloid-derived suppressor cells, Tregs, and metabolic pathways.
• Targeting key immunosuppressive mediators and angiogenesis to reverse immunosuppression.
• Exploring nanoparticle- and drug-based approaches and combination therapies with immune checkpoint inhibitors.
• Nanomedicine approaches to metabolically reshape immunosuppressive microenvironments, stromal cell interactions, and nutrient competition dynamics
• Validating predictive biomarkers like serum cytokines, neutrophil-to-lymphocyte ratios, and liquid biopsy-based circulating tumor DNA for treatment response monitoring.
• Investigating immunogenomic profiles and characterization through single-cell sequencing, AI-driven computational models, and related approaches.
• Engineered cell therapies (CAR-T/NK/M), cancer vaccines, tumor antigen loss, and epigenetic modulators to overcome drug resistance.
• Studying tumor heterogeneity, clonal evolution, and microenvironmental adaptations driving therapeutic escape.
• Implementing biomarker-guided clinical trial designs and real-time adaptive therapies using liquid biopsy data and pharmacogenomic profiling to minimize adverse events.

Please note that manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by robust and relevant validation (clinical cohort or biological validation in vitro or in vivo) are out of scope for this Research Topic.