TY  - EJOU
AU  - Litkowska, Aleksandra 
AU  - Grenda, Anna 
AU  - Krawczyk, Paweł 

TI  - Immune Mechanisms and Stem Cells in Early-Stage Non-Small Cell Lung Cancer: A Systematic Review
T2  - Oncology Research

PY  - 
VL  - 
IS  - 
SN  - 1555-3906

AB  - Objectives: Early-stage non-small cell lung cancer (NSCLC) may represent a period during which interactions between emerging tumor cells and the immune system influence subsequent disease progression. This systematic review aimed to summarize current evidence on immune dynamics, tumor microenvironment (TME) remodeling, immune evasion mechanisms, and the potential implications of these processes for early therapeutic intervention. Methods: A systematic literature search was conducted in PubMed, Scopus, and Google Scholar for studies published between 1998 and 2026. Original articles, reviews, experimental studies, and clinical trials published in English were included if they addressed tumor immunology, the TME, immune evasion, or cancer stem cells (CSCs) in early-stage NSCLC. Studies focused exclusively on advanced disease, lacking relevance to the review topic, presenting insufficient methodological quality, or representing duplicate data were excluded. Following the screening process, 112 publications were included in the review. Results: The available evidence indicates that immune surveillance in early NSCLC involves complex and context-dependent interactions among T lymphocytes, natural killer cells, and macrophages. Progressive TME remodeling may contribute to a shift from anti-tumor immune activity toward immunosuppressive conditions through metabolic alterations and recruitment of regulatory immune populations. CSCs have been proposed as contributors to tumor heterogeneity and immune resistance, although their clinical significance remains under investigation. Disturbances in antigen presentation and activation of immune checkpoint pathways, including PD-1/PD-L1 (Programmed Cell Death Protein 1/Programmed Death-Ligand 1), were identified as key mechanisms of immune evasion. Preliminary clinical evidence suggests that neoadjuvant immunotherapy may provide benefit when applied in earlier stages of NSCLC, although further validation is required. Conclusion: Current evidence suggests that early immune alterations in NSCLC may influence tumor evolution and therapeutic responsiveness. Improved understanding of these processes could support optimization of perioperative treatment strategies; however, the clinical implications of many findings remain uncertain and require further investigation.
KW  - Non-small cell lung cancer; immune surveillance; cancer stem cells; tumor microenvironment (TME); immune evasion; therapeutic window

DO  - 10.32604/or.2026.082451