ABSTRACT:
Lung cancer remains the leading cause of cancer-related deaths worldwide, and its interaction with the tumor immune microenvironment is a decisive factor in tumor progression and therapeutic outcomes. The advent of immunotherapies, particularly immune checkpoint inhibitors targeting PD-1 and PD-L1, has transformed treatment paradigms and intensified research into the complex interplay between immune cells, stromal components, and tumor cells. Understanding these interactions is essential for identifying predictive and prognostic biomarkers, optimizing immunotherapy strategies, and advancing precision oncology. This study explores global research trends, collaboration patterns, and emerging themes in tumor immune microenvironment and immunotherapy studies in lung cancer, with emphasis on their translational and clinical significance. Publications from 2000 to 2025 were retrieved from Web of Science, Scopus, and PubMed. Analyses using VOSviewer, R Bibliometrix, and CiteSpace evaluated publication growth, leading countries, institutions, authors, and journals. Keyword co-occurrence and thematic mapping identified research hotspots and forecasted future directions. Results reveal a sharp rise in publications after 2014, aligning with breakthroughs in PD-1/PD-L1-targeted therapies. The United States and China dominate in output and international collaboration, with major cancer centers driving multidisciplinary research. Key topics include PD-1/PD-L1 pathways, tumor-infiltrating lymphocytes, tumor-associated macrophages, tumor mutational burden, and mechanisms of immunotherapy resistance. Emerging directions highlight tertiary lymphoid structures, microbiome influences on the tumor immune microenvironment, and the integration of spatial transcriptomics and single-cell technologies for detailed immune profiling. This analysis underscores the intertwined growth of tumor immune microenvironment and immunotherapy research in lung cancer. Advances in biomarker evaluation, supported by immunohistochemistry, multiplex assays, and spatial profiling, combined with digital pathology and AI-assisted analysis, are set to enhance diagnostic precision, guide treatment selection, and improve patient outcomes.