• bioinformatics
• immune cell infiltration
• immune-related genes
• lung adenocarcinoma
• prognosis

• CD163
• CD68
• IL-1RA
• IL-6
• M1
• M2
• bronchoalveolar lavage fluid
• cytokines
• cytokines profile
• lung cancer microenvironment
• macrophages

• statutory grant number 488 Military Institute of Medicine- National Research Institute

Lymphocytes play a leading role in regulation of the immune system in lung cancer patients. The recognition of T cells profile may help in prediction of effectiveness of anticancer immunotherapy. The aim of the study was to determine the dominant subpopulation of CD4+ and CD8+ lymphocytes in metastatic and non-metastatic lymph nodes (LNs) of lung cancer patients. LNs aspirates were obtained during EBUS/TBNA procedure and cells were analyzed by flow cytometry. We showed a higher percentage of CD4+ and CD8+ effector memory T cells in the metastatic than in the non-metastatic LNs (28.6 vs. 15.3% and 28.6 vs. 14.0%, p< 0.05). The proportion of CD45RO+ T regulatory cells (CD45RO+ Tregs) was higher in the metastatic LNs than in the non-metastatic ones (65.6 vs. 31%, p< 0.05). We reported the significant differences in T cell subsets depending on the lung cancer metastatic process. We observed that the effector memory T cells were predominant subpopulations in metastatic LNs. Lymphocyte profile in LNs is easy to evaluate by flow cytometry of EBUS/TBNA samples and may reflect the immune status in lung cancer.

• Humans
• Leukocyte Common Antigens
• Lung Neoplasms
• Lymph Nodes
• Memory T Cells
• T-Lymphocytes, Regulatory/pathology

• Wojskowy Instytut Medyczny

• Cancer immunotherapy
• Dendritic cell
• Dendritic-cell vaccination
• Lung cancer
• Monocyte
• Tumour microenvironment

• Cancer stem cells
• EBUS/TBNA
• Lung cancer
• Lymph nodes
• T cells

• B7-H1 Antigen/pharmacology
• B7-H1 Antigen/therapeutic use
• Carcinoma, Non-Small-Cell Lung/immunology
• Carcinoma, Non-Small-Cell Lung/pathology
• Female
• Humans
• Immunotherapy/methods
• Lung Neoplasms/immunology
• Lung Neoplasms/pathology
• Lymph Nodes/pathology
• Lymphatic Metastasis
• Male
• Neoplastic Stem Cells/pathology
• Tumor Microenvironment/immunology

• Cancer stem cells
• EBUS/TBNA
• EpCAM
• Lung cancer
• PD-L1

We investigated the local immune status and its prognostic value in lung adenocarcinoma. In total, 513 lung adenocarcinoma samples from TCGA and ImmPort databases were collected and analyzed. The R package coxph was employed to mine immune-related genes that were significant prognostic indicators using both univariate and multivariate analyses. The R software package glmnet was then used for Lasso Cox regression analysis, and a prognosis prediction model was constructed for lung adenocarcinoma; clusterProfiler was selected for functional gene annotations and KEGG enrichment analysis. Finally, correlations between the RiskScore and clinical features or signaling pathways were established. Sixty-four immune-related genes remarkably correlated with patient prognosis and were further applied. Samples were hierarchically clustered into two subgroups. Accordingly, the LASSO regression algorithm was employed to screen the 14 most representative immune-related genes (PSMD11, PPIA, MIF, BMP5, DKK1, PDGFB, ANGPTL4, IL1R2, THRB, LTBR, TNFRSF1, TNFRSF17, IL20RB, and MC1R) with respect to patient prognosis. Then, the prognosis prediction model for lung adenocarcinoma patients (namely, the RiskScore equation) was constructed, and the training set samples were incorporated to evaluate the efficiency of this model to predict and classify patient prognosis. Subsequently, based on functional annotations and KEGG pathway analysis, the 14 immune-related genes were mainly enriched in pathways closely associated with lung adenocarcinoma and its immune microenvironment, such as cytokine–cytokine receptor interaction and human T-cell leukemia virus 1 infection. Furthermore, correlations between the RiskScore and clinical features of the training set samples and signaling pathways (such as p53, cell cycle, and DNA repair) were also demonstrated. Finally, the test set sample data were employed for independent testing and verifying the model. We established a prognostic prediction RiskScore model based on the expression profiles of 14 immune-related genes, which shows high prediction accuracy and stability in identifying immune features. This could provide clinical guidance for the diagnosis and prognosis of different immunophenotypes, and suggest multiple targets for precise advanced lung adenocarcinoma therapy based on subtype-specific immune molecules.

• hierarchal clustering
• immunophenotypes
• lung adenocarcinoma
• patient prognosis
• riskscore

Lung cancer remains a serious oncological problem worldwide. The delayed diagnosis and a prevalence of advanced stages in up to 70% of cases at recognition are still observed. Thanks to targeted therapies and immunotherapy a significant progress in achieving prolonged survival in some lung cancer patients is reported. A precise histopathological diagnosis, especially the recognition of adenocarcinoma, and a progress in the methods of clinical staging underlie the proper qualification of patients for a tailored therapy. The deep molecular characteristics of lung cancer in liquid biopsy, for example blood, bronchoalveolar lavage fluid (BALF), cell suspension from needle aspirates, are currently available. The molecular characteristic has recently been extended with molecular aberrations of BRAF, KRAS, MET, ERBB2, RET, NTRK next to the well-known EGFR mutations and ALK, ROS-1 relocation. The present paper discusses the usefulness of adequate pathological methods and molecular testing for the identification of a broad spectrum of predictive biomarkers for a molecular-directed lung cancer therapy. Immunotherapy with immune checkpoint inhibitors (ICIs) is approved in the first line therapy of advanced non-small-cell lung cancer. To date only PD-L1 expression on tumor cells has been found to be a marker of response to ICIs. The efficacy of ICIs as well as the susceptibility to immune-related adverse events are highly individual, so immune biomarkers are widely investigated. The candidates for predictive factors for ICIs immunotherapy include cancer cell antigenicity, presence of regulatory/suppressory molecules on cancer cells, cancer stem cells or on exosomes, and, on the other hand, an immune status of the patient. Cancers with high immune infiltration in the tumor milieu, referred to as “hot” tumors, seem to ensure a better response to ICIs than the “cold” ones. BALF analysis may replace cancer tissue examination, which is of limited access in advanced stages, for the recognition of the nature of immune response in the tumor environment. Tumor mutational burden (TMB) was shown to correlate with a good response to ICIs, especially when combined with other anticancer therapies. The present paper demonstrates the results of recent studies on lung cancer characteristics which bring us closer to the definition of useful prognostic/predictive factors.

• EGFR
• PD-L1
• TME
• immunohistochemistry
• immunotherapy
• lung cancer
• molecular pathology
• molecular testing

Nowadays, cancer immunotherapy is a promising strategy in solid tumour treatment. It has become a breakthrough in achieving long-term survival in many advanced cases. The essence of modern immunotherapy is to improve the host antitumour immune defence. Currently, it is critically important to determine the biomarkers that could be helpful in planning this type of individual therapy. It has turned out that an important prognostic factor is the evaluation of inflammatory infiltration of the tumour mass, including the characteristics of populations of lymphocytes and macrophages, and the expression of suppressive and regulatory molecules. For lung cancer, <30% of the tumours are resectable and available for a complete microscopic examination. In other cases, the material for the study of inflammatory infiltration may be a tumour biopsy, but this is of limited importance. A valuable way to evaluate the microenvironment of tumour growth is a bronchoalveolar lavage (BAL) fluid examination. In the BAL fluid, the cellular and noncellular components determine the specific type of inflammatory response in an environment of developing cancer. BAL fluid analysis may be a valuable addition to peripheral blood analysis during qualification for modern immunomodulatory therapy. Moreover, it is important material to seek biomarkers of clinical significance.

Bronchoalveolar lavage may be used to evaluate the immune status of lung cancer patients before immunotherapyhttp://ow.ly/lXRi30dzmGY