Emerging roles of T helper 17 and regulatory T cells in lung cancer progression and metastasis

Abstract

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.

Change of Peripheral Blood Treg/Thl7 in Cognitive Impairment with Chronic Renal Failure Patients

“…The Treg/Th17 balance plays a key role in maintaining the stability of the immune state [9, 10]. An imbalance can cause a series of immune inflammatory responses that are characteristic of cancer, autoimmune diseases, atherosclerosis, allergic asthma and diseases of the development process [11-15]. Clinical studies have found that the presence of Treg cells in patients undergoing dialysis for end-stage renal failure significantly reduced the frequency of cellular and functional damage and significantly increased the Th17 cell frequency [16].…”

Human lung tumor FOXP+ Tregs upregulate four “Treg-locking” transcription factors

“…Lung cancers (LC) are the leading cause of deaths from cancer (1)(2)(3)(4). FOXP3 + Tregs are thought to facilitate tumor growth and metastases by inhibition of antitumor immunity (5)(6)(7)(8), and accumulation of Tregs within cancers usually corresponds with poor outcomes (4,6,9), although exceptions are known (10)(11)(12).…”

“…FOXP3 + Tregs are thought to facilitate tumor growth and metastases by inhibition of antitumor immunity (5)(6)(7)(8), and accumulation of Tregs within cancers usually corresponds with poor outcomes (4,6,9), although exceptions are known (10)(11)(12). These inconsistencies suggest that mere enumeration of tumor-infiltrating FOXP3 + cells may not be sufficiently incisive for understanding the biology of Tregs in clinical oncology.…”

Somatic mutation-associated T follicular helper cell elevation in lung adenocarcinoma

“…Expression of plasma cell markers were also found to be increased in tumour samples compared to normal (FC = 2.87) (Figure 1A). While Tregs and M0 macrophages have been extensively described in lung cancer, 18,19 Tfh cells remains relatively understudied.

10.1080/2162402X.2018.1504728-F0001Figure 1. Relative expression of immune cell subsets in bulk gene expression data . A) CIBERSORT was used to deconvolve cell fractions of 22 immune cell subsets in matched tumour (n = 83) and normal (n = 83) samples, and the tumour to normal ratio of each cell type was calculated per each matched pair and the mean across the cohort calculated.

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