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Immune Landscape and Prognostic Index for Pancreatic Cancer: A Study Based on TCGA Database and in vivo Validation
37 Pages Posted: 14 Feb 2022
More...Abstract
Background: The immune microenvironment of pancreatic cancer plays a vital role in its occurrence and development. At present, the immunotherapy efficacy on pancreatic cancer remains unsatisfactory. Therefore, it is still of necessity to further clarify the pancreatic immune cell infiltration and search for immune-related prognostic indicators.
Methods: We employed the R software to analyze the 135 PAAD patients’ data retrieved from the TCGA database. “CIBERSORT” and “estimateScore” packages were used to calculate the immune cell infiltration and TME score, followed by correlation analyses of the immune cells. Unsupervised clustering was performed using the R package “ConsensusClusterPlus” to identify prognostic immune clusters and differentially expressed genes clusters. The principal component analysis in R was used to calculate the immune score. The R package “survival” and “survminer” were used to identify immune score and immune cells proportion survival differences. The function of immune cells was verified through datasets in the GEO database and in vivo experiments.
Result: The correlation analysis results showed that M0 Macrophages were negatively correlated with activated dendritic cells, CD8+ T cells, and immune scores. There was a positive correlation between CD8+ T cells and immune score. There were differences in median survival in ICI clusters, gene clusters, and immune score groups (p < 0.05). The results showed that M0 macrophages accounted for more than 9.8%, indicating a poor prognosis, while T cells accounted for more than 9.2%, indicating a good prognosis. In vivo results showed that M0 macrophages promote pancreatic cancer growth.
Conclusion: Immune score and M0 proportion are prognostic predictors for PAAD. M0 macrophages promoted pancreatic cancer growth in vivo. Elimination of M0 macrophages may be a promising strategy against PAAD.
Funding: This study was supported by Anhui Provincial Key Research and Development Plan
(202104a07020021); the Shanghai Municipal Health Commission (20184Y0370);
Declaration of Interest: All of the authors declared there are no conflicts of interests for this manuscript.
Ethical Approval: The study protocol was approved by the committee on the ethics of animal experiments of Fudan university shanghai cancer center (No. FUSCC-IACUC-2021540).
Keywords: Pancreatic cancer, Immune landscape, Prognosis, M0 macrophage
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