Open Access
Review
04 November 2025Therapeutic Vaccination in Lung Cancer: Past Attempts, Current Approaches and Future Promises
Lung cancer represents a significant burden on global health, necessitating the need for new and effective treatment strategies that expand our current therapeutic repertoire. Immunotherapy, namely immune checkpoint blockade (ICB), has revolutionized lung cancer therapy over the last decade by invigorating anti-tumor T cell responses to prolong survival and quality of life. However, not all patients benefit from ICB, emphasizing the need for novel immunotherapeutic strategies that engage other immune functionalities to offer synergy with already available therapies. There has been a longstanding interest in deploying lung cancer vaccines to generate or enhance tumor antigen-specific T cell responses for greater tumor control. Thus far, success has been limited to early-stage clinical trials, where safety, generation of antigen-specific T cell responses in blood sampling, and some patient benefits have been established. Moving forward, the establishment of widespread clinical success in large-scale trials is a necessity to bring lung cancer vaccines into the therapeutic arsenal. In this review, we examine the logic and mechanisms behind therapeutic lung cancer vaccines, before critically and iteratively examining past and current attempts in lung cancer vaccinology. We also look at early pre-clinical studies and outline the future for therapeutic lung cancer vaccines.
Open Access
Article
27 November 2025Lyz1-Expressing Alveolar Type II Cells Contribute to Lung Regeneration
The alveolar units, composed of alveolar epithelial type II cells (AT2) and type I cells (AT1), are essential for efficient gas exchange. While AT2 cells are known to play critical roles in alveolar homeostasis and regeneration, the contribution of heterogeneous AT2 cells to lung repair remains poorly understood. Here, we identified a distinct AT2 subpopulation that exclusively expressed Lysozyme 1 (Lyz1) through single-cell RNA sequencing (scRNA-seq) analyses. Cell fate mapping revealed that the Lyz1CreERT2 mouse strain specifically labeled Lyz1-expressing AT2 cells in vivo at homeostasis. Following lung injury, Lyz1+ AT2 cells expanded and contributed to alveolar regeneration by generating both self-renewing AT2 cells and differentiating AT1 cells. We further observed the emergence of de novo Lyz1-expressing cells in the airways after lung injury. Additionally, Lyz1+ AT2 cells displayed significantly enhanced proliferative capacity compared with general bulk AT2 cells in 3D organoid cultures. These findings define Lyz1+ AT2 cells as a previously unrecognized progenitor population, expanding the paradigm of alveolar regeneration and providing insight into how epithelial diversity supports lung regeneration.
Open Access
Review
10 December 2025Intracellular Chloride Channels: A Rising Target in Lung Disease Research
Chloride intracellular ion channels (CLICs) represent a relatively underexplored class of chloride channels and are included in a research initiative that focuses on druggable genes that have not been well studied yet. As a unique family, CLICs exist in membrane and soluble forms and play a role in regulating chloride flux and modulating various aspects of cellular biology. To date, six mammalian CLICs have been cloned and characterized at molecular and physiological levels. The respiratory system, responsible for gas exchange between the atmosphere and the human body, has recently been shown to express CLICs with functional relevance in lung pathophysiology, including lung carcinoma, inflammation, and endothelial dysfunction. Notably, the expression patterns of CLIC isoforms in lung cell types are distinct. Among them, CLIC1, CLIC3, and CLIC4 have been investigated more extensively, particularly in the context of lung cancer, inflammatory diseases, and pulmonary arterial hypertension. A deeper understanding of the role of CLICs in regulating lung cellular function may pave the way for developing novel therapeutic strategies to treat pulmonary disorders. In this review, we summarize the expression and functional roles of CLICs in lung pathophysiology, with particular emphasis on CLIC1, CLIC3, and CLIC4.
