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Characterization of the Immune Cell Infiltration Profile in Pancreatic Carcinoma to Aid in Immunotherapy

The tumor microenvironment (TME) is comprised of tumor cells, infiltrating immune cells, and stroma. Multiple reports suggest that the immune cell infiltration (ICI) in TME is strongly associated with responsiveness to immunotherapy and prognosis of certain cancers. Thus far, the ICI profile of panc...

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Autores principales: Luo, De, Kuang, Fei, Du, Juan, Zhou, Mengjia, Peng, Fangyi, Gan, Yu, Fang, Cheng, Yang, Xiaoli, Li, Bo, Su, Song
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155731/
https://www.ncbi.nlm.nih.gov/pubmed/34055645
http://dx.doi.org/10.3389/fonc.2021.677609
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author Luo, De
Kuang, Fei
Du, Juan
Zhou, Mengjia
Peng, Fangyi
Gan, Yu
Fang, Cheng
Yang, Xiaoli
Li, Bo
Su, Song
author_facet Luo, De
Kuang, Fei
Du, Juan
Zhou, Mengjia
Peng, Fangyi
Gan, Yu
Fang, Cheng
Yang, Xiaoli
Li, Bo
Su, Song
author_sort Luo, De
collection PubMed
description The tumor microenvironment (TME) is comprised of tumor cells, infiltrating immune cells, and stroma. Multiple reports suggest that the immune cell infiltration (ICI) in TME is strongly associated with responsiveness to immunotherapy and prognosis of certain cancers. Thus far, the ICI profile of pancreatic carcinoma (PC) remains unclear. Here, we employed two algorithms to characterize the ICI profile of PC patients. Based on our results, we identified 2 ICI patterns and calculated the ICI score by using principal component analysis. Furthermore, we revealed that patients with low ICI scores had a better prognosis, compared to high ICI scores. Moreover, we discovered that a low tumor mutation burden (TMB) offered better overall survival (OS), relative to high TMB. In this study, a high ICI score referred to elevated PD-L1/TGF-β levels, increased activation of cell cycle pathway and DNA repair pathway, as well as reduced expression of immune-activation-related genes. We also demonstrated that three metabolic pathways were suppressed in the low ICI score group. These data may explain why a high ICI score equates to a poor prognosis. Based on our analysis, the ICI score can be used as an effective predictor of PC prognosis. Hence, establishing an ICI profile, based on a large patient population, will not only enhance our knowledge of TME but also aid in the development of immunotherapies specific to PC.
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spelling pubmed-81557312021-05-28 Characterization of the Immune Cell Infiltration Profile in Pancreatic Carcinoma to Aid in Immunotherapy Luo, De Kuang, Fei Du, Juan Zhou, Mengjia Peng, Fangyi Gan, Yu Fang, Cheng Yang, Xiaoli Li, Bo Su, Song Front Oncol Oncology The tumor microenvironment (TME) is comprised of tumor cells, infiltrating immune cells, and stroma. Multiple reports suggest that the immune cell infiltration (ICI) in TME is strongly associated with responsiveness to immunotherapy and prognosis of certain cancers. Thus far, the ICI profile of pancreatic carcinoma (PC) remains unclear. Here, we employed two algorithms to characterize the ICI profile of PC patients. Based on our results, we identified 2 ICI patterns and calculated the ICI score by using principal component analysis. Furthermore, we revealed that patients with low ICI scores had a better prognosis, compared to high ICI scores. Moreover, we discovered that a low tumor mutation burden (TMB) offered better overall survival (OS), relative to high TMB. In this study, a high ICI score referred to elevated PD-L1/TGF-β levels, increased activation of cell cycle pathway and DNA repair pathway, as well as reduced expression of immune-activation-related genes. We also demonstrated that three metabolic pathways were suppressed in the low ICI score group. These data may explain why a high ICI score equates to a poor prognosis. Based on our analysis, the ICI score can be used as an effective predictor of PC prognosis. Hence, establishing an ICI profile, based on a large patient population, will not only enhance our knowledge of TME but also aid in the development of immunotherapies specific to PC. Frontiers Media S.A. 2021-05-13 /pmc/articles/PMC8155731/ /pubmed/34055645 http://dx.doi.org/10.3389/fonc.2021.677609 Text en Copyright © 2021 Luo, Kuang, Du, Zhou, Peng, Gan, Fang, Yang, Li and Su https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Luo, De
Kuang, Fei
Du, Juan
Zhou, Mengjia
Peng, Fangyi
Gan, Yu
Fang, Cheng
Yang, Xiaoli
Li, Bo
Su, Song
Characterization of the Immune Cell Infiltration Profile in Pancreatic Carcinoma to Aid in Immunotherapy
title Characterization of the Immune Cell Infiltration Profile in Pancreatic Carcinoma to Aid in Immunotherapy
title_full Characterization of the Immune Cell Infiltration Profile in Pancreatic Carcinoma to Aid in Immunotherapy
title_fullStr Characterization of the Immune Cell Infiltration Profile in Pancreatic Carcinoma to Aid in Immunotherapy
title_full_unstemmed Characterization of the Immune Cell Infiltration Profile in Pancreatic Carcinoma to Aid in Immunotherapy
title_short Characterization of the Immune Cell Infiltration Profile in Pancreatic Carcinoma to Aid in Immunotherapy
title_sort characterization of the immune cell infiltration profile in pancreatic carcinoma to aid in immunotherapy
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155731/
https://www.ncbi.nlm.nih.gov/pubmed/34055645
http://dx.doi.org/10.3389/fonc.2021.677609
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