Cancer stem cells (CSCs) play a critical role in tumor recurrence, metastasis, and resistance to both chemotherapy and immunotherapy, owing to their unique biological properties.

Research highlights the importance of understanding CSCs in tumor progression and therapy resistance, emphasizing their contribution to immune evasion and metastatic spread.

Targeting key signaling pathways and molecular interactions involved in CSC-immune cell crosstalk is crucial for developing effective therapies.

Mechanisms of crosstalk between CSCs and immune cells—such as cytokines, exosomes, and metabolic intermediates—are vital for understanding tumor immune evasion.

Signaling pathways like Wnt/β-catenin, Hedgehog, Notch, JAK/STAT, TGF/SMAD, and PI3K/AKT/mTOR regulate CSC stemness and contribute to therapeutic resistance.

Interactions between CSCs and immune cells, including tumor-associated macrophages and regulatory T cells, create a tumor microenvironment that promotes immune evasion and chemoresistance.

CSCs possess a distinct glycocalyx profile with hyaluronan, heparan sulfate, and sialylated glycans that facilitate immune evasion and tumor survival.

Advances in techniques like single-cell omics, CRISPR screening, and patient-derived organoids are enhancing our understanding and treatment of CSCs in precision medicine.

Integrating CSC-targeted approaches with standard treatments is essential for enhancing clinical outcomes and preventing relapse in resistant cancers.

This research underscores the importance of understanding immune dynamics within tumor microenvironments and metastatic niches, focusing on CSC interactions.

Challenges such as standardizing organoid cultures, replicating tumor microenvironments, and addressing CSC plasticity complicate therapeutic strategies.

Emerging biomarkers like CD44, CD133, ALDH1, and EpCAM, along with targeted therapies such as CAR-T cells and miRNA modulation, hold promise for disrupting CSC resilience.

Clinical strategies that combine conventional therapies with interventions targeting CSC-immune interactions aim to improve immunotherapy outcomes and overcome resistance.