Rewiring Cancer from the Outside In: Tumor Immune Crosstalk, Stemness, and Therapy Resistance

Abstract:Cancer progression is shaped by continuous communication between malignant cells and the surrounding tumor microenvironment. This communication involves immune cells, stromal populations, endothelial cells, extracellular matrix components, soluble mediators, and extracellular vesicles. Among these interactions, tumor immune crosstalk plays a central role in regulating cancer cell plasticity, immune evasion, metastatic competence, and therapeutic response.Tumor associated macrophages and other immune components can promote tumor supportive conditions through cytokines, chemokines, growth factors, metabolites, and vesicle mediated signaling. These signals may drive macrophage polarization, suppress anti tumor immunity, and reshape cancer cell identity. At the same time, cancer cells can educate immune and stromal cells, creating feedback loops that support tumor growth, invasion, metastasis, and resistance to therapy.A key outcome of this extracellular communication is the emergence or maintenance of cancer stem like states. Cancer stem like cells are associated with self renewal, tumor initiation, metastatic recurrence, immune escape, and resistance to chemotherapy, targeted therapy, radiotherapy, and immunotherapy. Increasing evidence suggests that these phenotypes are not fixed, but can be induced or sustained by tumor microenvironmental signals, including inflammation, hypoxia, metabolic stress, immune cell derived mediators, and extracellular vesicle cargo.This Research Topic aims to bring together mechanistic and translational studies exploring how extracellular signals within the tumor ecosystem regulate tumor immune communication, cancer stem like reprogramming, disease progression, metastasis, and therapy resistance. We welcome studies using diverse solid tumor models, patient derived systems, organoids, co-culture platforms, in vivo models, and clinically relevant samples that connect tumor microenvironment biology with cancer cell intrinsic programs and therapeutic vulnerabilities.Scope:This Research Topic focuses on the cellular and molecular mechanisms through which extracellular signals in the tumor microenvironment regulate cancer cell behavior, immune crosstalk, stem like phenotypes, metastatic progression, and treatment response.Topics of interest include, but are not limited to:- Cancer cell communication with tumor-associated macrophages and other immune populations- Molecular mechanisms of macrophage polarization and tumor promoting immune states- Cytokine, chemokine, growth factor, metabolite, and extracellular vesicle signaling in the tumor microenvironment- Tumor immune crosstalk regulating cancer cell survival, plasticity, invasion, and metastasis- Extracellular signals driving cancer stem like cell identity, self renewal, and tumor initiating capacity- Macrophage and immune cell mediated regulation of cancer stemness and epithelial mesenchymal plasticity- Interactions between cancer stem like cells and immune, stromal, endothelial, or extracellular matrix components- Hypoxia, inflammation, metabolic stress, and niche derived signals supporting tumor progression and therapy resistance- Extracellular vesicle cargo involved in immune suppression, stemness acquisition, metastatic competence, or treatment escape- Mechanisms linking tumor associated macrophages or cancer stem like phenotypes to resistance against chemotherapy, targeted therapy, radiotherapy, and immunotherapy- Biomarkers of tumor immune crosstalk, macrophage activity, cancer stemness, prognosis, or therapeutic response- Therapeutic strategies targeting macrophage polarization, immune cell recruitment, extracellular signaling pathways, cancer stem like states, or tumor ecosystem vulnerabilities- Mechanistic studies using cell culture, co-culture systems, organoids, patient derived models, animal models, single cell approaches with validation, or clinical samplesSubmissions should provide clear mechanistic or translational insight into cancer cell biology, tumor–immune communication, and disease progression. Studies that are purely descriptive, rely only on bioinformatic analysis without experimental or clinical validation, or lack a clear connection to cancer cell behavior fall outside the preferred scope of this collection. Topic editors: Xudong Zhu, Jin-Ming Yang Source: https://www.frontiersin.org/research-topics/85546/rewiring-cancer-from-the-outside-in-tumor-immune-crosstalk-stemness-and-therapy-resistance