Immune cell analyses of the tumor microenvironment in prostate cancer highlight infiltrating regulatory <scp>T</scp> cells and macrophages as adverse prognostic factors

Andersen, Line B; Nørgaard, Maibritt; Rasmussen, Martin; Fredsøe, Jacob; Borre, Michael; Ulhøi, Benedicte Parm; Sørensen, Karina Dalsgaard

doi:10.1002/path.5757

Cited by 47 publications

(52 citation statements)

References 45 publications

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“…Likewise, TME analysis demonstrated that the high-PDLIM2 expression group displayed a higher microenvironment score, immune score, and stromal score than the low-PDLIM2 expression group. In agreement with this, it has been reported that PRAD patients in the high immune infiltration group exhibit poorer survival [ 32 ]. This result may be the main reason for poor survival in patients in the high-PDLIM2 expression group.…”

Section: Discussionsupporting

confidence: 83%

“…Immune cells in the tumor microenvironment play a vital role in the progression of PRAD [ 32 , 33 ], and PDLIM2 has been reported [ 34 ] to participate in immune process. Therefore, whether PDLIM2 expression was correlated with immune infiltration levels in PRAD was investigated via Spearman's correlation analysis in the pancaner TCGA database through the “xCell” algorithm [ 35 ].…”

Section: Resultsmentioning

confidence: 99%

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High Expression of PDLIM2 Predicts a Poor Prognosis in Prostate Cancer and Is Correlated with Epithelial-Mesenchymal Transition and Immune Cell Infiltration

Piao

Zheng

et al. 2022

Journal of Immunology Research

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Purpose. To elucidate the clinical and prognostic role of PDZ and LIM domain protein (PDLIM) genes and the association to epithelial-mesenchymal transition (EMT) and immune cell infiltration in patients with prostate cancer (PRAD). Methods. The data of RNA-seq, DNA methylation, and clinical features of PRAD patients were collected from The Cancer Genome Atlas (TCGA) database to define the prognostic value of PDLIM gene expression and the association with EMT and immune cell infiltration. A tissue microarray including 134 radical prostatectomy specimens was served as validation by immunohistochemistry (IHC) staining analysis. Results. The mRNA levels of PDLIM1/2/3/4/6/7 were significantly downregulated, while PDLIM5 was upregulated in PRAD ( P < 0.05 ). High expression of PDLIM2 mRNA suggests poor progression free interval in PRAD patients. DNA methylation of PDLIM2 was correlated with its mRNA expression level, and that the cg22973076 methylation site in PDLIM2 was associated with shorter PFI ( P < 0.05 ) in PRAD. Single-sample gene-set enrichment and gene functional enrichment results showed that PDLIM2 was correlated with EMT and immune processes. Spearman’s test showed a significant correlation with six reported EMT signatures and several EMT signature-related genes. Tumor microenvironment analysis revealed that the PDLIM2 mRNA expression was positively correlated with the immune score, stromal score, and various tumor infiltrating immune cells. Additionally, the results showed that patients in the high-PDLIM2 mRNA expression group may be more sensitive to immune checkpoint blockade therapy. Finally, IHC analysis further implicated the protein level of PDLIM2 was upregulated in PRAD and acts as a novel potential biomarker in predicting tumor progression. Conclusion. Our study suggests that PDLIM family genes might be significantly correlated with oncogenesis and the progression of PRAD. PDLIM2 correlated with EMT and immune cell infiltration by acting as an oncogene in PRAD, which may serve as a potential prognostic biomarker for PRAD patients.

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Section: Discussionsupporting

confidence: 83%

Section: Resultsmentioning

confidence: 99%

High Expression of PDLIM2 Predicts a Poor Prognosis in Prostate Cancer and Is Correlated with Epithelial-Mesenchymal Transition and Immune Cell Infiltration

Piao

Zheng

et al. 2022

Journal of Immunology Research

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“…CD204 is not M2 specific, and CD163 might be suitable for M2-like marker 22 . In recent article, high number of CD163-positive cells was related to poor clinical course in prostate cancer, however, M1 cells were also associated to poor clinical course 23 . In breast cancer, the data that cancer-derived factor induced CD204 expression in cultured macrophages rather than CD163 and CD204 + cells predicted poor clinical course rather than CD163 indicated that CD204 might be a marker for protumor phenotype more suitable than CD163 in some organs 24 .…”

Section: Discussionmentioning

confidence: 96%

CD8-positive T cells and CD204-positive M2-like macrophages predict postoperative prognosis of very high-risk prostate cancer

Yanai

Kosaka

Mikami

et al. 2021

Sci Rep

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To stratify the heterogeneity of prostate cancer (PCa) with seminal vesicle invasion (SVI) immunologically after radical prostatectomy focusing on the tumor microenvironment. We retrospectively reviewed the clinicopathological data of 71 PCa patients with SVI, which is known as a factor of very high-risk PCa. Preoperative clinical variables and postoperative pathological variables were evaluated as predictors of biochemical recurrence (BCR) with a multivariate logistic regression. Immune cell infiltration including the CD8-positive cell (CD8+ cell) and CD204-positive M2-like macrophage (CD204+ cell) was investigated by immunohistochemistry. The cumulative incidence and risk of BCR were assessed with a Kaplan–Meier analysis and competing risks regression. A higher CD8+ cell count in the SVI area significantly indicated a favorable prognosis for cancers with SVI (p = 0.004). A lower CD204+ cell count in the SVI area also significantly indicated a favorable prognosis for cancers with SVI (p = 0.004). Furthermore, the combination of the CD8+ and CD204+ cell infiltration ratio of the SVI area to the main tumor area was a significant factor for BCR in the patients with the PCa with SVI (p = 0.001). In PCa patients with SVI, the combination of CD8+ and CD204+ cell infiltration is useful to predict the prognosis.

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“…In PCa, several studies reported that more TAM infiltration in the TME promoted PCa cell proliferation and migration and was associated with PSA failure or PCa progression after hormonal therapy [ 49 , 50 ]. In fact, increased infiltration of TAMs often predicts poor prognosis in patients with mPCa [ 51 , 52 ]. On the one hand, it has been reported that TAM-secreted CCL5 can promote PCa cell migration, invasion, and epithelial-mesenchymal transition (EMT) by activating β-catenin/STAT3 signaling [ 53 ].…”

Section: Discussionmentioning

confidence: 99%

CircSMARCC1 facilitates tumor progression by disrupting the crosstalk between prostate cancer cells and tumor-associated macrophages via miR-1322/CCL20/CCR6 signaling

Xie

et al. 2022

Mol Cancer

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Background Circular RNAs (circRNAs) mediate the infiltration of tumor-associated macrophages (TAMs) to facilitate carcinogenesis and development of various types of cancers. However, the role of circRNAs in regulating macrophages in prostate cancer (PCa) remains uncertain. Methods Differentially expressed circRNAs in PCa were identified by RNA sequencing. The expression of circSMARCC1 was recognized and evaluated using fluorescence in situ hybridization and quantitative real-time PCR. The oncogenic role of circSMARCC1 in PCa tumor proliferation and metastasis was investigated through a series of in vitro and in vivo assays. Finally, Western blot, biotin-labeled RNA pulldown, luciferase assay, rescue experiments, and co-culture experiments with TAMs were conducted to reveal the mechanistic role of circSMARCC1. Results CircSMARCC1 was dramatically up-regulated in PCa cells, plasma and tissues. Overexpression of circSMARCC1 promotes tumor proliferation and metastasis both in vitro and in vivo, whereas knockdown of circSMARCC1 exerts the opposite effects. Mechanistically, circSMARCC1 regulates the expression of CC-chemokine ligand 20 (CCL20) via sponging miR-1322 and activate PI3K-Akt signaling pathway involved in the proliferation and epithelial mesenchymal transformation. More importantly, high expression of circSMARCC1 was positively associated with colonization of CD68+/CD163+/CD206+ TAMs in tumor microenvironment. In addition, overexpression of circSMARCC1 facilitates the expression of CD163 in macrophages through the CCL20-CCR6 axis, induces TAMs infiltration and M2 polarization, thereby leading to PCa progression. Conclusions CircSMARCC1 up-regulates the chemokine CCL20 secretion by sponging miR-1322, which is involved in the crosstalk between tumor cells and TAMs by targeting CCL20/CCR6 signaling to promote progression of PCa.

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Immune cell analyses of the tumor microenvironment in prostate cancer highlight infiltrating regulatory T cells and macrophages as adverse prognostic factors

Cited by 47 publications

References 45 publications

High Expression of PDLIM2 Predicts a Poor Prognosis in Prostate Cancer and Is Correlated with Epithelial-Mesenchymal Transition and Immune Cell Infiltration

High Expression of PDLIM2 Predicts a Poor Prognosis in Prostate Cancer and Is Correlated with Epithelial-Mesenchymal Transition and Immune Cell Infiltration

CD8-positive T cells and CD204-positive M2-like macrophages predict postoperative prognosis of very high-risk prostate cancer

CircSMARCC1 facilitates tumor progression by disrupting the crosstalk between prostate cancer cells and tumor-associated macrophages via miR-1322/CCL20/CCR6 signaling

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