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Immune and Inflammatory Cell Composition of Human Lung Cancer Stroma.

Banat GA, Tretyn A, Pullamsetti SS, Wilhelm J, Weigert A, Olesch C, Ebel K, Stiewe T, Grimminger F, Seeger W, Fink L, Savai R - PLoS ONE (2015)

Bottom Line: In human lung cancer sections we observed a significant elevation/infiltration of total-T lymphocytes (CD3+), cytotoxic-T cells (CD8+), T-helper cells (CD4+), B cells (CD20+), macrophages (CD68+), mast cells (CD117+), mononuclear cells (CD11c+), plasma cells, activated-T cells (MUM1+), B cells, myeloid cells (PD1+) and neutrophilic granulocytes (myeloperoxidase+) compared with healthy donor specimens.We observed all of these immune cell markers in different types of lung cancers including squamous cell carcinoma, adenocarcinoma, adenosquamous cell carcinoma, small cell carcinoma, papillary adenocarcinoma, metastatic adenocarcinoma, and bronchioloalveolar carcinoma.The numbers of all tumor-associated immune cells (except MUM1+ cells) in stage III cancer specimens was significantly greater than those in stage I samples.

View Article: PubMed Central - PubMed

Affiliation: Internal Medicine, University of Giessen and Marburg Lung Center, Member of the German Center for Lung Research, Giessen, Germany.

ABSTRACT
Recent studies indicate that the abnormal microenvironment of tumors may play a critical role in carcinogenesis, including lung cancer. We comprehensively assessed the number of stromal cells, especially immune/inflammatory cells, in lung cancer and evaluated their infiltration in cancers of different stages, types and metastatic characteristics potential. Immunohistochemical analysis of lung cancer tissue arrays containing normal and lung cancer sections was performed. This analysis was combined with cyto-/histomorphological assessment and quantification of cells to classify/subclassify tumors accurately and to perform a high throughput analysis of stromal cell composition in different types of lung cancer. In human lung cancer sections we observed a significant elevation/infiltration of total-T lymphocytes (CD3+), cytotoxic-T cells (CD8+), T-helper cells (CD4+), B cells (CD20+), macrophages (CD68+), mast cells (CD117+), mononuclear cells (CD11c+), plasma cells, activated-T cells (MUM1+), B cells, myeloid cells (PD1+) and neutrophilic granulocytes (myeloperoxidase+) compared with healthy donor specimens. We observed all of these immune cell markers in different types of lung cancers including squamous cell carcinoma, adenocarcinoma, adenosquamous cell carcinoma, small cell carcinoma, papillary adenocarcinoma, metastatic adenocarcinoma, and bronchioloalveolar carcinoma. The numbers of all tumor-associated immune cells (except MUM1+ cells) in stage III cancer specimens was significantly greater than those in stage I samples. We observed substantial stage-dependent immune cell infiltration in human lung tumors suggesting that the tumor microenvironment plays a critical role during lung carcinogenesis. Strategies for therapeutic interference with lung cancer microenvironment should consider the complexity of its immune cell composition.

No MeSH data available.


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Immunohistochemical analysis and quantification of CD8-positive T lymphocytes in human lung cancer.Human lung cancer tissue array was stained with CD8 antibody to detect cytotoxic T lymphocytes. (A) Quantification of CD8+ cells in lung cancer vs. healthy donor specimens. (B–E) Quantification of CD8+ cells based on (B) their pathology, (C) cancer stage, (D) tumor size, and (E) nodal status. Cell numbers are given as CD8-positive cells per 1000 cells. (F) Representative images of human lung sections stained with CD8 antibody based on their pathology. Scale bar = 25 μm.
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pone.0139073.g004: Immunohistochemical analysis and quantification of CD8-positive T lymphocytes in human lung cancer.Human lung cancer tissue array was stained with CD8 antibody to detect cytotoxic T lymphocytes. (A) Quantification of CD8+ cells in lung cancer vs. healthy donor specimens. (B–E) Quantification of CD8+ cells based on (B) their pathology, (C) cancer stage, (D) tumor size, and (E) nodal status. Cell numbers are given as CD8-positive cells per 1000 cells. (F) Representative images of human lung sections stained with CD8 antibody based on their pathology. Scale bar = 25 μm.

Mentions: To further evaluate the distribution of T lymphocyte subpopulations, sections were analyzed by immunostaining for the prevalence of T helper (CD4+) and cytotoxic (CD8+) T cells. As shown in Fig 3A, the number of CD4+ cells was significantly increased in tumor tissue compared with healthy donor tissue [62 (52…72) vs. 12 (4…32)]. The prevalence of T helper cells was independent of cancer type (Fig 3B and 3F), however the number of infiltrating cells was higher in stage III cancer compared with stage I [113 (102…125) vs. 22 (12…42), Fig 3C]. The number of CD4+ T lymphocytes in tumor samples was independent of tumor size [T2: 62 (52…75] vs. T3: 60 (32…114)] and nodal status [N0: 63 (51…77) vs. N1+2: 60 (43…83), Fig 3D and 3E]. Similar results were obtained for infiltrating cytotoxic T lymphocytes, with a higher number of CD8+ cells in tumor tissues compared with healthy controls [80 (69…93) vs. 17 (7…41)] and higher CD8+ cell infiltration in stage III vs. stage I lung cancer [132 (114…154) vs. 51 (27…98), Fig 4A and 4C]. There was no correlation between the prevalence of cytotoxic T cells and cancer type, tumor size or nodal status (Fig 4B, 4D and 4E).


Immune and Inflammatory Cell Composition of Human Lung Cancer Stroma.

Banat GA, Tretyn A, Pullamsetti SS, Wilhelm J, Weigert A, Olesch C, Ebel K, Stiewe T, Grimminger F, Seeger W, Fink L, Savai R - PLoS ONE (2015)

Immunohistochemical analysis and quantification of CD8-positive T lymphocytes in human lung cancer.Human lung cancer tissue array was stained with CD8 antibody to detect cytotoxic T lymphocytes. (A) Quantification of CD8+ cells in lung cancer vs. healthy donor specimens. (B–E) Quantification of CD8+ cells based on (B) their pathology, (C) cancer stage, (D) tumor size, and (E) nodal status. Cell numbers are given as CD8-positive cells per 1000 cells. (F) Representative images of human lung sections stained with CD8 antibody based on their pathology. Scale bar = 25 μm.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4587668&req=5

pone.0139073.g004: Immunohistochemical analysis and quantification of CD8-positive T lymphocytes in human lung cancer.Human lung cancer tissue array was stained with CD8 antibody to detect cytotoxic T lymphocytes. (A) Quantification of CD8+ cells in lung cancer vs. healthy donor specimens. (B–E) Quantification of CD8+ cells based on (B) their pathology, (C) cancer stage, (D) tumor size, and (E) nodal status. Cell numbers are given as CD8-positive cells per 1000 cells. (F) Representative images of human lung sections stained with CD8 antibody based on their pathology. Scale bar = 25 μm.
Mentions: To further evaluate the distribution of T lymphocyte subpopulations, sections were analyzed by immunostaining for the prevalence of T helper (CD4+) and cytotoxic (CD8+) T cells. As shown in Fig 3A, the number of CD4+ cells was significantly increased in tumor tissue compared with healthy donor tissue [62 (52…72) vs. 12 (4…32)]. The prevalence of T helper cells was independent of cancer type (Fig 3B and 3F), however the number of infiltrating cells was higher in stage III cancer compared with stage I [113 (102…125) vs. 22 (12…42), Fig 3C]. The number of CD4+ T lymphocytes in tumor samples was independent of tumor size [T2: 62 (52…75] vs. T3: 60 (32…114)] and nodal status [N0: 63 (51…77) vs. N1+2: 60 (43…83), Fig 3D and 3E]. Similar results were obtained for infiltrating cytotoxic T lymphocytes, with a higher number of CD8+ cells in tumor tissues compared with healthy controls [80 (69…93) vs. 17 (7…41)] and higher CD8+ cell infiltration in stage III vs. stage I lung cancer [132 (114…154) vs. 51 (27…98), Fig 4A and 4C]. There was no correlation between the prevalence of cytotoxic T cells and cancer type, tumor size or nodal status (Fig 4B, 4D and 4E).

Bottom Line: In human lung cancer sections we observed a significant elevation/infiltration of total-T lymphocytes (CD3+), cytotoxic-T cells (CD8+), T-helper cells (CD4+), B cells (CD20+), macrophages (CD68+), mast cells (CD117+), mononuclear cells (CD11c+), plasma cells, activated-T cells (MUM1+), B cells, myeloid cells (PD1+) and neutrophilic granulocytes (myeloperoxidase+) compared with healthy donor specimens.We observed all of these immune cell markers in different types of lung cancers including squamous cell carcinoma, adenocarcinoma, adenosquamous cell carcinoma, small cell carcinoma, papillary adenocarcinoma, metastatic adenocarcinoma, and bronchioloalveolar carcinoma.The numbers of all tumor-associated immune cells (except MUM1+ cells) in stage III cancer specimens was significantly greater than those in stage I samples.

View Article: PubMed Central - PubMed

Affiliation: Internal Medicine, University of Giessen and Marburg Lung Center, Member of the German Center for Lung Research, Giessen, Germany.

ABSTRACT
Recent studies indicate that the abnormal microenvironment of tumors may play a critical role in carcinogenesis, including lung cancer. We comprehensively assessed the number of stromal cells, especially immune/inflammatory cells, in lung cancer and evaluated their infiltration in cancers of different stages, types and metastatic characteristics potential. Immunohistochemical analysis of lung cancer tissue arrays containing normal and lung cancer sections was performed. This analysis was combined with cyto-/histomorphological assessment and quantification of cells to classify/subclassify tumors accurately and to perform a high throughput analysis of stromal cell composition in different types of lung cancer. In human lung cancer sections we observed a significant elevation/infiltration of total-T lymphocytes (CD3+), cytotoxic-T cells (CD8+), T-helper cells (CD4+), B cells (CD20+), macrophages (CD68+), mast cells (CD117+), mononuclear cells (CD11c+), plasma cells, activated-T cells (MUM1+), B cells, myeloid cells (PD1+) and neutrophilic granulocytes (myeloperoxidase+) compared with healthy donor specimens. We observed all of these immune cell markers in different types of lung cancers including squamous cell carcinoma, adenocarcinoma, adenosquamous cell carcinoma, small cell carcinoma, papillary adenocarcinoma, metastatic adenocarcinoma, and bronchioloalveolar carcinoma. The numbers of all tumor-associated immune cells (except MUM1+ cells) in stage III cancer specimens was significantly greater than those in stage I samples. We observed substantial stage-dependent immune cell infiltration in human lung tumors suggesting that the tumor microenvironment plays a critical role during lung carcinogenesis. Strategies for therapeutic interference with lung cancer microenvironment should consider the complexity of its immune cell composition.

No MeSH data available.


Related in: MedlinePlus