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The Expression And Significance Of Tumor-Infiltrating Lymphocytes And Chemokines CXCL5 And CXCL10 In Pancreatic Cancer

Posted on:2019-06-27Degree:MasterType:Thesis
Country:ChinaCandidate:B WuFull Text:PDF
GTID:2404330602958916Subject:Surgery
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BackgroundPancreatic ductal adenocarcinoma?PDAC?is one of the most malignant tumors.Recently researchers have found that the tumor microenvironment plays an important role in tumors.Tumor infiltrating lymphocytes?TILs?are involved in the anti-tumor immune response.The types,numbers and distribution of TILs are closely related to the prognosis of cancer patients.However,the infiltration of TILs in tumor tissue is affected by many factors,one of the major reasons is the expression of chemokines in tumor tissues.Objective1.To analyze the distribution of CD4+T and CD8+T lymphocyte infiltration in pancreatic cancer and its correlation with clinicopathological features,and to analyze the prognosis of pancreatic cancer.Reveal the relationship between lymphocyte infiltration and prognosis in different parts of tumor tissue.2.To analyze the expression of CXCL5 and CXCL10 in pancreatic cancer and its relationship with clinicopathological features and prognosis.Methods1.The infiltration of CD4+,CD8+T lymphocytes in 143 patients with PDAC was detected by immunohistochemistry.Two variables,Intratumoral infiltration and Intraepith-elial attack,were set to evaluate the spatial distribution of TILs infiltration in pancreatic cancer.And analyze its relationship with clinical pathological factors and prognosis.2.Immunohistochemistry was used to detect the expression of CXCL5 and CXCL10in 119 patients with PDAC.Compare the difference between the expression of cancer tissue and adjacent normal tissue.And analyze its relationship with clinical pathological factors and prognosis.Results1.In tumor tissues,the proportion of CD8+T intratumoral infiltration high than that of CD4+T intratumoral infiltration high.However,there was no significant difference between CD8+T intratumoral infiltration high and CD4+T intratumoral infiltration high in normal tissues?p=0.000?.2.In the tumor nests,the proportion of CD8+T intraepithelial attack yes than that of CD4+T intraepithelial attack yes?p=0.000?.3.The proportion of CD8+T intratumoral infiltration high,CD4+T intratumoral infiltration high in tumor tissues than that in adjacent normal tissues?p=0.004?0.000?.4.In tumor tissue,the infiltration state of CD4+T showed distinctive characteristics,can be divided into 4 types:?1?CD4+T intratumoral infiltration low and CD4+T intraepithelial attack no,Ilow/Ano;?2?CD4+T intratumoral infiltration low and CD4+T intraepithelial attack yes,Ilow/Ayes;?3?CD4+T intratumoral infiltration high and CD4+T intraepithelial attack no,Ihigh/Ano;?4?CD4+T intratumoral infiltration high and CD4+T intraepithelial attack yes,Ihigh/Ayes.This feature also appears in the infiltration state of CD8+T:?1?CD8+T intratumoral infiltration low and CD8+T intraepithelial attack no,Ilow/Ano;?2?CD8+T intratumoral infiltration low and CD8+T intraepithelial attack yes,Ilow/Ayes;?3?CD8+T intratumoral infiltration high and CD8+T intraepithelial attack no,Ihigh/Ano;?4?CD8+T intratumoral infiltration high and CD8+T intraepithelial attack yes,Ihigh/Ayes.5.The correlation between CD4+T intratumoral infiltration and T staging was signify-cant.CD4+T intratumoral infiltration high correlated with higher T stage.And CD4+T intratumoral infiltration had no significant correlation with other clinicopathological featu-res.There was a negative correlation between CD4+T intraepithelial attack and vascular invasion and no significant correlation with other clinicopathological features.6.The correlation between CD8+T intratumoral infiltration and T staging was signify-cant.CD8+T intratumoral infiltration high correlated with higher T stage.And CD8+T intratumoral infiltration had no significant correlation with other clinicopatholog-ical features.There was no significant correlation between CD8+T intraepithelial attack and clinicopathological features.7.There was a positive correlation between CD8+T intratumoral infiltration with CD4+T intratumoral infiltration and CD4+T intraepithelial attack;there was a positive correlation between CD8+T intraepithelial attack with CD4+T intratumoral infiltration,CD4+T intraepithelial attack and CD8+T intratumoral infiltration.8.CD4+T intratumoral infiltration,CD4+T intraepithelial attack,CD8+T intratumoral infiltration were not an independent prognostic factor for patients with pancreatic cancer.CD8+T intraepithelial attack is an independent prognostic factor for prognosis of pancre-atic cancer patients.9.Among the four subtypes of infiltrating CD8+T lymphocytes,the best to worst prognosis were CD8+T Ilow/Ayes,CD8+T Ihigh/Ayes,CD8+T Ilow/Ano,CD8+T Ihigh/Ano.This indicating that infiltration of CD8+T cells in cancer nest epithelium is beneficial to prognosis;The CD8+T Ilow/Ayes group was superior to the CD8+T Ihigh/Ayes group,while the CD8+T Ilow/Ano group was superior to the CD8+T Ihigh/Ano group.These two phenom-ena can be speculated that simple CD8+T lymphocyte infiltration in tumor stroma may not play an antitumor effect.On the contrary,it is not conducive to the prognosis of patients.CD8+T lymphocyte infiltration in the cancer nest is beneficial to the prognosis.10.The expression of CXCL5 in pancreatic cancer tissues was higher than that in adjacent normal tissues.The expression of CXCL10 in pancreatic cancer tissues was higher than that in adjacent normal tissues.11.CXCL5 is an independent prognostic factor for patients with pancreatic cancer,associated with poor prognosis;CXCL10 is an independent prognostic factor for patients with pancreatic cancer,associated with poor prognosis.Conclusion1.In PDAC tissues,there are four distinct types of infiltrating state of CD8+T lymphocytes;CD8+T lymphocyte infiltration in tumor nests is an independent prognostic factor for pancreatic cancer patients,which is in favor of prognosis;In addition,Only CD8+T lymphocyte infiltration in the stroma outside the cancer nests without CD8+T lymphocyte infiltration in tumor nests may be detrimental to the prognosis of the patients.2.The expressions of CXCL5 and CXCL10 in pancreatic cancer tissues were higher than those in adjacent normal tissues.Both CXCL5 and CXCL10 were independent prognostic factors for patients with pancreatic cancer,which were all associated with poor prognosis.
Keywords/Search Tags:Pancreatic cancer, Tumor-infiltrating lymphocytes, Tumor microenvironment, CXCL5, CXCL10
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