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The Role of Neutrophils in Cancer Progression.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	The Role of Neutrophils in Cancer Progression./
作者:	Rohanizadeh, Ramin.
面頁冊數:	1 online resource (108 pages)
附註:	Source: Masters Abstracts International, Volume: 83-10.
Contained By:	Masters Abstracts International83-10.
標題:	Infections. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=29043318click for full text (PQDT)
ISBN:	9798209933922

The Role of Neutrophils in Cancer Progression.
Rohanizadeh, Ramin.

The Role of Neutrophils in Cancer Progression. - 1 online resource (108 pages)

Source: Masters Abstracts International, Volume: 83-10.

Thesis (M.Sc.)--McGill University (Canada), 2021.

Includes bibliographical references

High circulating neutrophil to lymphocyte ratio (NLR) has been shown to be associated with poor oncologic outcomes. This raises the question as to whether neutrophils play a causative role in driving tumor progression. Accordingly, the first aim of this project was to determine if high NLR in cancer patients is associated with tumor-promoting neutrophils. In this aim, we also studied the involvement of NETosis in lymph node metastasis.It has been shown that tumor-associated neutrophils (TANs) exhibit phenotypic diversity and plasticity. However, most of these studies were in animals using aggressive cancer cell lines. Therefore, in the second aim, we sought to identify how in cancer patients, neutrophil phenotypes change when cells migrate from bone marrow to blood and then to tumor, and how tumor influences neutrophil phenotypes.Aim 1: Determine the association of NLR with neutrophil phenotypes in patients with gastroesophageal adenocarcinomaMethods: Tissue microarrays consisting of tumor core, tumor periphery, healthy stomach, and metastatic and non-metastatic lymph nodes were constructed using post-operative samples from 175 patients with gastro-esophageal adenocarcinoma. Immunohistochemistry (IHC) and immunofluorescence (IF) imaging were used to quantify the number of neutrophils/lymphocytes and the level of expression of arginase (Arg1) and neutrophil elastase (NE) in neutrophils. Lowdensity (LDNs) and high-density (HDNs) neutrophils were also isolated from blood samples of patients and immunophenotyped. LDN is known to be a tumor-promoting phenotype of neutrophils.Results: Tumor NLR and percentage of circulating LDNs were higher in patients with elevated blood NLR (≥ 4). LDNs exhibited higher expression of CD66b, Arg1, and CXCR2 than HDNs. High expression of these biomarkers has been reported in other studies to promote pro-tumor activities of neutrophils. High NLR in tumor core was associated with decreased survival, whileNLR in peripheral area had no such association. Patients with elevated blood and tumor NLR demonstrated higher expression of Arg1 and NE in TANs. It has been reported in the literature that Arg1 suppresses anti-tumor immunity, and NE promotes tumor cell proliferation. Patients with nodal metastasis showed a higher number of neutrophils and neutrophil extracellular trap (NET) formation in their lymph nodes compared to those without nodal metastasis. In our study, higher NET formation, in both involved and uninvolved lymph nodes, was associated with poor survival.Conclusion: We showed that high blood and tumor NLRs were associated with neutrophils with tumor-promoting phenotypes in blood and tumor. We also demonstrated that nodal neutrophils and NETs may act as pre-metastatic promoter niche in lymph nodes of cancer patients.Aim 2: Determine the influence of tumor microenvironment on neutrophil phenotypeMethods: To compare neutrophil phenotypes in different body compartments, post-operative samples were collected from bone marrow, peripheral blood, human esophageal tumor, and healthy esophagus from 21 patients with esophageal adenocarcinoma. Neutrophils were immunophenotyped by flow cytometry using a panel of 12 biomarkers. Peripheral blood neutrophils (PBNs) from healthy volunteers were also treated with different cancer cellconditioned media (CM) using four human esophageal cancer cell lines.Results: TANs acquired an activated phenotype evidenced by increased CD66b, CD11b, and CD54 and decreased CD62L and CD16 expressions. TANs had a lower expression of NE in internal flow cytometry staining, which could be due to the degranulation of TANs. This assumption was supported in our study by increased Arg1 and NE positive areas in tumor samples compared to healthy tissue (using IF imaging). Increased CXCR4 and decreased CD62L expressions in TANs showed that TANs were aged compared to neutrophils in healthy tissue. CXCR2 expression decreased in TANs, probably due to the ligation of CXCR2 with proinflammatory factors in tumor. In vitro treating PBNs with CM resulted in the activation of PBNs.Conclusion: We showed that TANs acquired an activated phenotype compared to neutrophils isolated from other body compartments.

Electronic reproduction.
Ann Arbor, Mich. :
ProQuest,
2023

Mode of access: World Wide Web

ISBN: 9798209933922Subjects--Topical Terms:

1621997
Infections.
Index Terms--Genre/Form:

542853
Electronic books.

The Role of Neutrophils in Cancer Progression.
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502 $a Thesis (M.Sc.)--McGill University (Canada), 2021.
504 $a Includes bibliographical references
520 $a High circulating neutrophil to lymphocyte ratio (NLR) has been shown to be associated with poor oncologic outcomes. This raises the question as to whether neutrophils play a causative role in driving tumor progression. Accordingly, the first aim of this project was to determine if high NLR in cancer patients is associated with tumor-promoting neutrophils. In this aim, we also studied the involvement of NETosis in lymph node metastasis.It has been shown that tumor-associated neutrophils (TANs) exhibit phenotypic diversity and plasticity. However, most of these studies were in animals using aggressive cancer cell lines. Therefore, in the second aim, we sought to identify how in cancer patients, neutrophil phenotypes change when cells migrate from bone marrow to blood and then to tumor, and how tumor influences neutrophil phenotypes.Aim 1: Determine the association of NLR with neutrophil phenotypes in patients with gastroesophageal adenocarcinomaMethods: Tissue microarrays consisting of tumor core, tumor periphery, healthy stomach, and metastatic and non-metastatic lymph nodes were constructed using post-operative samples from 175 patients with gastro-esophageal adenocarcinoma. Immunohistochemistry (IHC) and immunofluorescence (IF) imaging were used to quantify the number of neutrophils/lymphocytes and the level of expression of arginase (Arg1) and neutrophil elastase (NE) in neutrophils. Lowdensity (LDNs) and high-density (HDNs) neutrophils were also isolated from blood samples of patients and immunophenotyped. LDN is known to be a tumor-promoting phenotype of neutrophils.Results: Tumor NLR and percentage of circulating LDNs were higher in patients with elevated blood NLR (≥ 4). LDNs exhibited higher expression of CD66b, Arg1, and CXCR2 than HDNs. High expression of these biomarkers has been reported in other studies to promote pro-tumor activities of neutrophils. High NLR in tumor core was associated with decreased survival, whileNLR in peripheral area had no such association. Patients with elevated blood and tumor NLR demonstrated higher expression of Arg1 and NE in TANs. It has been reported in the literature that Arg1 suppresses anti-tumor immunity, and NE promotes tumor cell proliferation. Patients with nodal metastasis showed a higher number of neutrophils and neutrophil extracellular trap (NET) formation in their lymph nodes compared to those without nodal metastasis. In our study, higher NET formation, in both involved and uninvolved lymph nodes, was associated with poor survival.Conclusion: We showed that high blood and tumor NLRs were associated with neutrophils with tumor-promoting phenotypes in blood and tumor. We also demonstrated that nodal neutrophils and NETs may act as pre-metastatic promoter niche in lymph nodes of cancer patients.Aim 2: Determine the influence of tumor microenvironment on neutrophil phenotypeMethods: To compare neutrophil phenotypes in different body compartments, post-operative samples were collected from bone marrow, peripheral blood, human esophageal tumor, and healthy esophagus from 21 patients with esophageal adenocarcinoma. Neutrophils were immunophenotyped by flow cytometry using a panel of 12 biomarkers. Peripheral blood neutrophils (PBNs) from healthy volunteers were also treated with different cancer cellconditioned media (CM) using four human esophageal cancer cell lines.Results: TANs acquired an activated phenotype evidenced by increased CD66b, CD11b, and CD54 and decreased CD62L and CD16 expressions. TANs had a lower expression of NE in internal flow cytometry staining, which could be due to the degranulation of TANs. This assumption was supported in our study by increased Arg1 and NE positive areas in tumor samples compared to healthy tissue (using IF imaging). Increased CXCR4 and decreased CD62L expressions in TANs showed that TANs were aged compared to neutrophils in healthy tissue. CXCR2 expression decreased in TANs, probably due to the ligation of CXCR2 with proinflammatory factors in tumor. In vitro treating PBNs with CM resulted in the activation of PBNs.Conclusion: We showed that TANs acquired an activated phenotype compared to neutrophils isolated from other body compartments.
520 $a Il a ete demontre dans la litterature qu'un rapport elevee de neutrophiles/lymphocytes (NLR) est associe a de mauvaisresultats oncologiques. Cela souleve la question de savoirsi les neutrophiles jouent un role causal dans la progression de la tumeur. En consequence, le premier objectif de ce projet etait de determiner si un NLR eleve chez les patients cancereux est associe a l'existence des neutrophilesfavorisant la tumeur. Dans ce but, nous avons egalement etudie l'implication de la NETosis ganglionnaire dans les metastases.Il a ete aussi demontre que les neutrophiles associes aux tumeurs (TAN) presentent une diversite phenotypique et une plasticite. Cependant, la plupart de ces etudes portaient sur des animaux, utilisant des lignees cellulaires cancereuses agressives. Par consequent, dans le deuxieme objectif, nous avons cherche a identifier comment, chez les patients cancereux, les phenotypes des neutrophiles changent lorsque les cellules migrent de la moelle osseuse versle sang puis vers la tumeur, et comment la tumeur influence les phenotypes des neutrophiles.Objectif 1: Determiner l'association du NLR avec les phenotypes neutrophiles chez les patients avec adenocarcinome gastro-oesophagienMethodes: Microarrays tissulaires constituees du noyau et de la peripherie de la tumeur, d'un estomac sain, et de ganglions lymphatiques metastatiques et non metastatiques ont ete construites des echantillons postoperatoires de 175 patients. L'imagerie par immunohistochimie (IHC) et immunofluorescence (IF) ont ete utilisees pour quantifier le nombre de neutrophiles/lymphocytes et le niveau d'expression de l'arginase (Arg1) et celle de l'elastase des neutrophiles (NE) dans les neutrophiles. Des neutrophiles de faible densite (LDN) et de haute densite (HDN) ont egalement ete isoles a partir d'echantillons sanguins de patients et ont ete immunophenotypes. Le LDN est connu pour etre un phenotype des neutrophiles favorisant la tumeur.Resultats: Le NLR tumoral et le % de LDN circulants etaient plus eleves chez les patients avec un NLR sanguin eleve (≥ 4). Les LDNs presentaient une expression plus elevee de CD66b, Arg1 et CXCR2 que les HDNs. Il a ete rapporte que l'expression elevee de ces biomarqueurs favorise les activites pro-tumorales des neutrophiles. Un NLR eleve dans le noyau de tumeur etait associe a une diminution de la survie, tandis que le NLR dans la zone peripherique de tumeur n'avait pas une telle association. Les patients avec un NLR sanguin et tumoral eleve ont demontres une expression plus elevee d'Arg1 et de NE dans les TANs. Il a ete rapporte que Arg1 supprime l'immunite anti-tumorale, et NE favorise la proliferation des cellules tumorales. Les patients presentant des metastases ganglionnaires ont montre un nombre plus eleve de neutrophiles et de formation de pieges extracellulaires des neutrophiles (NETs) dans leurs ganglions lymphatiques par rapport a ceux sans metastase ganglionnaire. Une formation plus elevee de NET, a la fois dans les ganglions lymphatiques positives et negatives, etait associee a une faible survie.Conclusion: Nous avons montre que des NLR sanguins et tumoraux eleves etaient associes a des neutrophiles favorisant la tumeur. Nous avons egalement demontre que les neutrophiles ganglionnaires et les NETs ganglionnaires peuvent agir comme une niche de promoteur premetastatique dans les ganglions lymphatiques.Objectif 2: Determiner l'influence du microenvironnement tumoral sur le phenotype des neutrophilesMethodes: Pour comparer les phenotypes des neutrophiles dans differents compartiments corporels, des echantillons postoperatoires ont ete preleves de la moelle osseuse, du sang peripherique, de la tumeur oesophagienne humaine et de l'oesophage sain de 21 patients. Les neutrophiles ont ete immunophenotypes par cytometrie en flux a l'aide d'un panel de 12 biomarqueurs. Les neutrophiles du sang peripherique (PBN) de volontaires sains ont egalement ete traites avec differents milieux conditionnes par des cellules cancereuses (CM) en utilisant quatre lignees cellulaires de cancer de l'oesophage humain.Resultats: Les TANs ont acquis un phenotype active mis en evidence par une augmentation des CD66b, CD11b et CD54 et une diminution des expressions de CD62L et CD16. Les TANs avaient une expression plus faible de NE demontre par cytometrie de flux, ce qui pourrait etre du a la degranulation des TANs. Cette hypothese etait etayee par une augmentation des zones positives pour Arg1 et NE dans la tumeur par rapport aux tissus sains (en imagerie IF). Une augmentation de CXCR4 et une diminution des expressions de CD62L ont demontre que les TANs etaient ages par rapport aux neutrophiles dans les tissus sains. L'expression de CXCR2 a diminue dans les TANs, probablement en raison de couplage de CXCR2 avec des facteurs pro-inflammatoires dans la tumeur. Le traitement in vitro des PBNs avec le CM a entraine l'activation des PBNs.Conclusion: les TANs ont acquis un phenotype active et pro-tumoral par rapport aux neutrophiles isoles d'autres compartiments corporels.
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