Cancer cell plasticity in the tumor immune niche: Historical context and emerging paradigms

Cancer biology research increasingly recognizes the profound heterogeneity and plasticity of cancer cells. These cells can transition dynamically between different phenotypic states, reprogramming their fate and identity through genetic and non-genetic changes in response to both tumor-intrinsic cues and extrinsic factors, such as those presented by the tumor immune microenvironment (TME). Recent studies have demonstrated that cancer cells gain new properties that enable them to become more stem-like, less differentiated, or more invasive, facilitating metastasis, immune evasion, and metabolic adaptation. Despite notable advances in cancer therapy, including targeted therapies and immunotherapies, many patients still experience disease progression or therapy resistance, underlining persistent gaps in our understanding of the mechanisms underlying these cellular state transitions.There is a growing body of evidence linking cancer cell plasticity to therapeutic resistance and immune escape. For example, research has identified specific signaling pathways, transcriptional networks, epigenetic regulators, and metabolic rewiring events that drive the emergence of aggressive or therapy-resistant phenotypes in both solid and hematological malignancies. Furthermore, the interplay between cancer cell states and the surrounding immune niche, including T cells and myeloid subsets, has emerged as a critical component shaping disease progression and treatment response. However, the precise molecular features and extrinsic signals guiding these phenotypic transitions—and their effects on the TME—remain incompletely defined, representing a major barrier to the development of effective and durable cancer therapies.This Research Topic aims to advance our understanding of how cancer cell plasticity influences therapy outcomes, alters immune cell functions and reshapes the tumor immune microenvironment, as well as to define the phenotypes and molecular mechanisms driving disease progression or resistance in various cancer types. The goal is to identify novel signaling pathways, gene regulatory circuits, and metabolic or epigenetic factors that underlie cancer cell reprogramming and the emergence of aggressive phenotypes, ultimately informing the development of therapies capable of preventing progression, overcoming resistance, and maximizing patient benefit.To gather further insights in the normal and pathological boundaries of cancer cell plasticity in both solid and hematological malignancies, we welcome articles addressing, but not limited to, the following themes:- Molecular and cellular mechanisms driving cancer plasticity and progression and the impact on immune cell function within the TME- Mechanisms altering immune cell functions and promoting immune suppression, tumor escape and resistance against immunotherapies, including immune checkpoint inhibitors and adoptive T cell therapies - Cancer cell phenotypes associated with disease initiation, progression, dormancy, and resistance to various therapies, including resistance to immune-mediated therapies and the effects on immune recognition and escape- Influence of inflammatory signals and cancer-derived growth factors in shaping the tumor immune niche, cancer and immune cell crosstalk, and therapeutic strategies that reverse immunosuppression and promote anti-tumor immunity- Metabolic adaptations and epigenetic regulation affecting cancer cell tolerance to therapy and immune cell functionality within the TME- Crosstalk and altered communication patterns between cancer and immune cells that drive disease progression and immune suppression- Emerging therapeutic strategies targeting cancer plasticity, reversing immunosuppression, promoting anti-tumor immunity, and overcoming therapy resistancePlease 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.Topic Editor Andrea Di Pietro declares having received funding resources for a project through the imCORE network (supported by Roche–Genentech). Topic editors: Reem Saleh, Sandhya Singh, Andrea Di Pietro Source: https://www.frontiersin.org/research-topics/79478/cancer-cell-plasticity-in-the-tumor-immune-niche-historical-context-and-emerging-paradigms