Advanced metastatic cancer poses utmost clinical challenges and may present molecular and cellular features distinct from an early-stage cancer. Herein, we present single-cell transcriptome profiling of metastatic lung adenocarcinoma, the most prevalent histological lung cancer type diagnosed at stage IV in over 40% of all cases. From 208,506 cells populating the normal tissues or early to metastatic stage cancer in 44 patients, we identify a cancer cell subtype deviating from the normal differentiation trajectory and dominating the metastatic stage. In all stages, the stromal and immune cell dynamics reveal ontological and functional changes that create a pro-tumoral and immunosuppressive microenvironment. Normal resident myeloid cell populations are gradually replaced with monocyte-derived macrophages and dendritic cells, along with T-cell exhaustion. This extensive single-cell analysis enhances our understanding of molecular and cellular dynamics in metastatic lung cancer and reveals potential diagnostic and therapeutic targets in cancer-microenvironment interactions.

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BackgroundThe gastrointestinal (GI) tract is one of the most common extranasal sites in extranodal NK/T-cell lymphoma (ENKTL). However, data regarding ENKTL involving the GI tract are relatively scarce. Thus, we performed a multicenter, multinational retrospective study to analyze clinical features and treatment outcomes of ENKTL involving the GI tract.Patients and methodsPatients with ENKTL involving the GI tract diagnosed in twelve participating centers between 1991 and 2012 were retrospectively analyzed from five Asian countries.ResultsThe analysis of 81 patients with ENKTL involving the GI tract revealed that more than 60% of patients presented as advanced disease with B symptoms. 55 patients (68%) had GI manifestations including abdominal pain (n = 26, 32%), GI tract bleeding (n = 17, 21%) and bowel perforation (n = 12, 15%). The most common GI site was the small intestine, including the jejunum and ileum (n = 57, 70.3%). There were 34 patients (42%) who received systemic chemotherapy while 33 patients (41%) underwent surgery plus chemotherapy. However, 35 patients (43%) died due to disease progression, and treatment-related mortality including sepsis occurred in 17 patients (21%). Thus, the median overall survival was 7.8 months (95% Confidence interval: 3.9 – 11.7 months). Patients who could undergo surgery plus chemotherapy showed a trend of better survival than those treated with chemotherapy alone.ConclusionOverall, the data indicated that ENKTL involving the GI tract has a dismal prognosis despite active treatment including chemotherapy and surgery. Thus, more effective treatment strategies are required for this disease entity.