Roles of Tumor Immune Microenvironment in Non-small Cell Lung Cancer

Lung cancer is the leading cause of cancer-related death. The prognosis is poor with 5-year relative survival of about 22%. Non-small cell lung cancer (NSCLC) comprises most cases of lung cancer. The tumor immune microenvironment (TIME) plays a critical role in NSCLC. Tumor mutational burden, immunogenic versus immunosuppressive tumors, and characteristics of premalignant lesions are tumor intrinsic factors defining the tumor and microenvironment interaction. Tumor-infiltrating immune cells and tertiary lymphoid structures are related to immune contexture. The location and compartments of immune cells within the tumor, the scoring method, and the whole slides versus tissue microarrays should be considered in TNM-Immunoscore staging. CD4+ T cells, follicular CD20+ B cells, activated B cells, natural killer cells, M1 macrophages, N1 neutrophils, and plasmacytoid dendritic cells are correlated with favorable outcomes. Exhausted B cells, M2 macrophages, N2 neutrophils, and myeloid-derived suppressor cells are associated with poorer results. There are variable results concerning CD8+ T lymphocytes and regulatory T cells. Understanding TIME helps define prognostic and predictive markers, identify patients who will benefit from different therapies, and improve treatment efficacy. Various cell markers of a specific cell type, distinct density, function, spatial pattern, and arrangement of immune cells, different histological types of NSCLC, stages, intra-tumoral versus tumor-stromal compartments, tumor-infiltration densities versus peripheral blood levels, treatment-naive assessments versus investigations during or after therapies, measurements made in the various time points after the initiation of treatments, and different treatment modalities are responsible for heterogeneous findings concerning the role of TIME components in NSCLC.