Aging, Epithelial Plasticity, and Immune Dysregulation in Lung and Solid Tumors

Aging is accompanied by a gradual remodeling of both the immune system and epithelial tissues. The aging immune system undergoes immunosenescence and inflammaging, characterized by reduced immune surveillance, impaired responses to new antigens, and a chronic, low-grade inflammatory state. In parallel, epithelial tissues show increased fragility, accumulation of DNA damage, altered stem/progenitor cell function, and a greater tendency toward plasticity, including shifts between differentiated, progenitor-like, and mesenchymal-like states. Together, these changes are thought to create a permissive environment for the initiation and progression of lung and other solid tumors, yet the mechanisms connecting aging immunity, epithelial plasticity, and cancer remain incompletely understood.

This Research Topic focuses on how age-related immune dysregulation interacts with epithelial plasticity to shape tumor development, progression, and therapeutic response in lung and solid tumors, with a strong emphasis on the aging and the immune system interface.

We welcome studies that explore how immunosenescence, inflammaging, and age-associated alterations in innate and adaptive immunity influence epithelial cell behavior in pre-malignant and malignant contexts. This includes work on how aging immune cells regulate epithelial–mesenchymal transition (EMT), partial or hybrid EMT states, stemness, senescence, and other plastic programs that drive tumor heterogeneity, invasion, metastasis, and resistance to therapy.

Particular interest is given to research that:

Dissects how chronic, age-related inflammation and immune dysfunction shape the tumor microenvironment and promote epithelial plasticity in lung and other solid cancers.

Examines crosstalk between aging immune cells (T cells, B cells, NK cells, macrophages, dendritic cells, and other myeloid populations) and epithelial/tumor cells, including cytokine and chemokine networks, checkpoint signaling, extracellular matrix remodeling, and metabolic competition.

Uses single-cell, spatial, and immune-profiling or multi-omic approaches to map age-associated changes in immune and epithelial compartments across the continuum from healthy tissue to pre-neoplastic lesions to established tumors.

Investigates how aging-related immune changes impact responses and resistance to immunotherapies, targeted agents, and cytotoxic treatments, particularly in relation to dynamic epithelial states and tumor evolution.

Identifies immune-based biomarkers, molecular pathways, or therapeutic targets that could enable age-informed risk stratification, prevention, and immunomodulatory or combination strategies in lung and solid tumors.

By integrating immunology, geroscience, and cancer biology, this topic aims to clarify how the aging immune system governs epithelial plasticity and tumor behavior, ultimately guiding the development of more precise, age-tailored interventions for patients with lung and other solid cancers.

Conflict of Interest: Dr Kiran Kundu is the Personal Investigator in ScaleReady’s G-Rex® Grant Award. SS

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Clinical Trial
• Data Report
• Editorial
• FAIR² Data
• FAIR² DATA Direct Submission
• General Commentary
• Hypothesis and Theory
• ... View all formats

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Clinical Trial
• Data Report
• Editorial
• FAIR² Data
• FAIR² DATA Direct Submission
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Systematic Review
• Technology and Code

Keywords: Immunosenescence, Epithelial plasticity, Inflammaging, Tumor microenvironment, Lung and solid tumors

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.