Lung cancer is a leading cause of cancer-related deaths worldwide. Lung cancer risk factors, including smoking and exposure to environmental carcinogens, have been linked to chronic inflammation. An integral feature of inflammation is the activation, expansion and infiltration of diverse immune cell types, including CD4+ T cells. Within this T cell subset are immunosuppressive regulatory T (Treg) cells and pro-inflammatory T helper 17 (Th17) cells that act in a fine balance to regulate appropriate adaptive immune responses.In the context of lung cancer, evidence suggests that Tregs promote metastasis and metastatic tumor foci development. Additionally, Th17 cells have been shown to be an integral component of the inflammatory milieu in the tumor microenvironment, and potentially involved in promoting distinct lung tumor phenotypes. Studies have shown that the composition of Tregs and Th17 cells are altered in the tumor microenvironment, and that these two CD4+ T cell subsets play active roles in promoting lung cancer progression and metastasis.We review current knowledge on the influence of Treg and Th17 cells on lung cancer tumorigenesis, progression, metastasis and prognosis. Furthermore, we discuss the potential biological and clinical implications of the balance among Treg/Th17 cells in the context of the lung tumor microenvironment and highlight the potential prognostic function and relationship to metastasis in lung cancer.

Arsenic is a well-known human carcinogen, which potentially affects ~160 million people worldwide via exposure to unsafe levels in drinking water. Lungs are one of the main target organs for arsenic-related carcinogenesis. These tumors exhibit particular features, such as squamous cell-type specificity and high incidence among never smokers. Arsenic-induced malignant transformation is mainly related to the biotransformation process intended for the metabolic clearing of the carcinogen, which results in specific genetic and epigenetic alterations that ultimately affect key pathways in lung carcinogenesis. Based on this, lung tumors induced by arsenic exposure could be considered an additional subtype of lung cancer, especially in the case of never-smokers, where arsenic is a known etiological agent. In this article, we review the current knowledge on the various mechanisms of arsenic carcinogenicity and the specific roles of this metalloid in signaling pathways leading to lung cancer.

The poor survival and recurrence rate in gastric adenocarcinoma highlights the need for cancer gene discovery. Towards this end, we globally assessed the expression of an emerging class of small non-coding RNAs, called PIWI-interacting RNAs (piRNAs). We analyzed the transcriptomes of 358 non-malignant stomach and gastric adenocarcinoma samples, and found that nearly half of the expressed piRNAs were overexpressed in tumours. Our gastric piRNA atlas showed that most piRNAs were embedded in protein-coding sequences rather than known piRNA clusters. Furthermore, we identified a three-piRNA signature associated with recurrence-free survival. In this proof-of-principle study, we demonstrate the potential clinical utility of piRNAs in gastric cancer.

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Gene function in cancer is often cell type-specific. The epithelial cell-specific transcription factor ELF3 is a documented tumor suppressor in many epithelial tumors yet displays oncogenic properties in others. Here, we show that ELF3 is an oncogene in the adenocarcinoma subtype of lung cancer (LUAD), providing genetic, functional, and clinical evidence of subtype specificity. We discover a region of focal amplification at chromosome 1q32.1 encompassing the ELF3 locus in LUAD which is absent in the squamous subtype. Gene dosage and promoter hypomethylation affect the locus in up to 80% of LUAD analyzed. ELF3 expression was required for tumor growth and a pan-cancer expression network analysis supports its subtype and tissue specificity. We further show that ELF3 displays strong prognostic value in LUAD but not LUSC. We conclude that, contrary to many other tumors of epithelial origin, ELF3 is an oncogene and putative therapeutic target in LUAD.