Abstract:Lung cancer is the leading cause of cancer mortality worldwide, and at only 18%, it has one of the lowest 5-year survival rates of all malignancies. With its highly complex mutational landscape, treatment strategies against lung cancer have proved largely ineffective. However with the recent success of immunotherapy trials in lung cancer, there is renewed enthusiasm in targeting the immune component of tumors. Macrophages make up the majority of the immune infiltrate in tumors and are a key cell type linking i… Show more
“…Immune cell composition in the tumor microenvironment may contribute to immune evasion and cancer development [36]. Innate and adaptive immune cells, including macrophages, neutrophils, natural killer (NK) cells and B cells, have been implicated in both anti-tumor and pro-tumor activities [37–43]. Specifically, the anti-tumor and pro-tumor roles of T cells in cancer development are currently of great interest.…”
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.
“…Immune cell composition in the tumor microenvironment may contribute to immune evasion and cancer development [36]. Innate and adaptive immune cells, including macrophages, neutrophils, natural killer (NK) cells and B cells, have been implicated in both anti-tumor and pro-tumor activities [37–43]. Specifically, the anti-tumor and pro-tumor roles of T cells in cancer development are currently of great interest.…”
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.
“…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.…”
T follicular helper cells (Tfh) play crucial roles in the development of humoral immunity. In the B cell-rich germinal center of lymphoid organs, they select for high-affinity B cells and aid in their maturation. While Tfh have known roles in B cell malignancies and have prognostic value in some epithelial cancers, their role in lung tumour initiation and development is unknown. Through immune cell deconvolution, we observed significantly increased Tfh in tumours from two independent cohorts of lung adenocarcinomas and found that this upregulation occurs early in tumour development. A subset of tumours were stained for T and B cells using multicolour immunohistochemistry, which revealed the presence of tumour-adjacent tertiary lymphoid organs in 17/20 cases each with an average of 16 Tfh observed in the germinal center. Importantly, Tfh levels were correlated with tumour mutational load and immunogenic cancer testis antigens, suggesting their involvement in mounting an active immune response against tumour neoantigens.
“…The link between inflammation and cancer development is particularly strong in patients with lung cancer, as the lungs are constantly exposed to environmental insults that may cause chronic inflammatory injuries and infection [10,11]. Currently, lung cancer is the leading cause of cancer-related deaths worldwide with 5-year survival rates averaging around only 15-18% [11,12]. Despite ongoing efforts to reduce smoking prevalence, cigarette smoking still remains the main cause of 90% of lung cancers [13,14] with ~15% of lifetime smokers developing the disease [14].…”
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