IL-9 Producing Tumor-Infiltrating Lymphocytes and Treg Subsets Drive Immune Escape of Tumor Cells in Non-Small Cell Lung Cancer.

Although lung cancer is the leading cause of cancer deaths worldwide, the mechanisms how lung cancer cells evade the immune system remain incompletely understood. Here, we discovered IL-9-dependent signaling mechanisms that drive immune evasion in non-small cell lung cancer (NSCLC). We found increased IL-9 and IL-21 production by T cells in the tumoral region of the lung of patients with NSCLC, suggesting the presence of Th9 cells in the lung tumor microenvironment.

Increased expression of the immunosuppressive interleukin-35 in patients with non-small cell lung cancer.

Background: The immunosuppressive role of the cytokine IL-35 in patients with non-small cell lung cancer (NSCLC) is poorly understood. In this study, we analysed the localisation and regulation of IL-35 in the lung of patients with non-small cell lung cancer (NSCLC) to further elucidate the immune-escape of cancer cells in perioperative course of disease.

Methods: Interleukin 35 (IL-35) was measured by ELISA in postoperative serum from 7 patients with NSCLC as well as 8 samples from healthy controls.

STAT1 deficiency supports PD-1/PD-L1 signaling resulting in dysfunctional TNFα mediated immune responses in a model of NSCLC.

In this study we described that Signal Transducer and Activator of Transcription 1 (STAT1) is a key point regulator of PD-1 in tumour infiltrating lymphocytes and PD-L1 in Tumour associated macrophages (TAM) in NSCLC. In our murine model of adenocarcinoma targeted deletion of Stat1 was found associated with enhanced tumour growth, impaired differentiation into M1-like macrophages from the bone marrow, the accumulation of tumor associated macrophages overexpressing PD-L1 and impaired T cell responses in the tumor microenvironment by affecting TNFα responses. In our human NSCLC patient cohort we found that loss of isoforms STAT1 α and STAT1β mRNA in the tumoural region of the lung correlates with increased tumor size in NSCLC patients.

NFATc1 Promotes Antitumoral Effector Functions and Memory CD8 T-cell Differentiation during Non-Small Cell Lung Cancer Development.

Nuclear factor of activated T cells 1 (NFATc1) is a transcription factor activated by T-cell receptor (TCR) and Ca signaling that affects T-cell activation and effector function. Upon tumor antigen challenge, TCR and calcium-release-activated channels are induced, promoting NFAT dephosphorylation and translocation into the nucleus. In this study, we report a progressive decrease of NFATc1 in lung tumor tissue and in tumor-infiltrating lymphocytes (TIL) of patients suffering from advanced-stage non-small cell lung cancer (NSCLC).

Interleukin-10-regulated tumour tolerance in non-small cell lung cancer.

Background: Lung cancer is the most life-threatening cancer type worldwide. Treatment options include surgery, radio- and chemotherapy, as well as the use of immunomodulatory antibodies. Interleukin (IL)-10 is an immunosuppressive cytokine involved in tumour immune escape.

Enhanced Acid Sphingomyelinase Activity Drives Immune Evasion and Tumor Growth in Non-Small Cell Lung Carcinoma.

The lipid hydrolase enzyme acid sphingomyelinase (ASM) is required for the conversion of the lipid cell membrane component sphingomyelin into ceramide. In cancer cells, ASM-mediated ceramide production is important for apoptosis, cell proliferation, and immune modulation, highlighting ASM as a potential multimodal therapeutic target. In this study, we demonstrate elevated ASM activity in the lung tumor environment and blood serum of patients with non-small cell lung cancer (NSCLC).

FAM13A is associated with non-small cell lung cancer (NSCLC) progression and controls tumor cell proliferation and survival.

Genome-wide association studies (GWAS) associated Family with sequence similarity 13, member A (FAM13A) with non-small cell lung cancer (NSCLC) occurrence. Here, we found increased numbers of FAM13A protein expressing cells in the tumoral region of lung tissues from a cohort of patients with NSCLC. Moreover, FAM13A inversely correlated with CTLA4 but directly correlated with HIF1α levels in the control region of these patients.