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Immune phenotypes of prostate cancer cells: Evidence of epithelial immune cell-like transition?

ABSTRACT: Prostate cancers (PCa) have been reported to actively suppress antitumor immune responses by creating an immune-suppressive microenvironment. There is mounting evidence that PCas may undergo an ''Epithelial Immune Cell-like Transition'' (EIT) by expressing molecules conventionally associated with immune cells (e.g., a variety of cytokines/receptors, immune transcription factors, Ig motifs, and immune checkpoint molecules), which subsequently results in the suppression of anti-cancer immune activity within the tumor microenvironment. Recent progress within the field of immune therapy has underscored the importance of immune checkpoint molecules in cancer development, thus leading to the development of novel immunotherapeutic approaches. Here, we review the expression of select immune checkpoint molecules in PCa epithelial and associated immune cells, with particular emphasis on clinical data supporting the concept of an EIT-mediated phenotype in PCa. Furthermore, we summarize current advances in anti-immune checkpoint therapies, and provide perspectives on their potential applicability.

SUBMITTER: Lin D

PROVIDER: S-EPMC5730833 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Immune phenotypes of prostate cancer cells: Evidence of epithelial immune cell-like transition?

Lin Dong D Wang Xinya X Choi Stephen Yiu Chuen SYC Ci Xinpei X Dong Xin X Wang Yuzhuo Y

Asian journal of urology 20160820 4

Prostate cancers (PCa) have been reported to actively suppress antitumor immune responses by creating an immune-suppressive microenvironment. There is mounting evidence that PCas may undergo an ''Epithelial Immune Cell-like Transition'' (EIT) by expressing molecules conventionally associated with immune cells (e.g., a variety of cytokines/receptors, immune transcription factors, Ig motifs, and immune checkpoint molecules), which subsequently results in the suppression of anti-cancer immune activ ...[more]

PMID: 29264187

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Project description:Initiation, growth, recurrence, and metastasis of head and neck squamous cell carcinomas (HNSCC) have been related to the behavior of cancer stem cells (CSC) that can be identified by their aldehyde-dehydrogenase-isoform-1 (ALDH1) activity. We quantified and enriched ALDH1(+) cells within HNSCC cell lines and subsequently characterized their phenotypical and functional properties like invasion capacity and epithelial-mesenchymal transition (EMT). Spheroid culture enriched CSC from five HNSCC cell lines by up to 5-fold. In spheroid-derived cells (SDC) and the parental monolayer-derived cell line ALDH1, CD44, CD24, E-Cadherin, α-SMA, and Vimentin expression was compared by flow-cytometry and immunofluorescence together with proliferation and cell cycle analysis. Invasion activity was evaluated by Matrigel assay and expression of stemness-related transcription factors (TF) Nanog, Oct3/4, Sox2 and EMT-related genes Snail1 and 2, and Twist by real-time PCR. All cell lines formed spheroids that could self-renew and be serially re-passaged. ALDH1 expression was significantly higher in SDC. ALDH1(+) cells showed increased colony-formation. The proportion of cells with a putative CSC marker constellation of CD44(+)/CD24(-) was highly variable (0.5% to 96%) in monolayer and spheroid cultures and overlapped in 0%-33% with the CD44(+)/CD24(-)/ALDH1(+) cell subset. SDC had significantly higher invading activity. mRNA of the stemness-related genes Sox2, Nanog, and Oct3/4 was significantly increased in SDC of all cell lines. Twist was significantly increased in two while Snail2 showed a significant increase in one and a significant decrease in SDC of two cell lines. SDC had a higher G0 phase proportion, showed high-level expression of α-SMA and Vimentin, but significantly decreased E-Cadherin expression. HNSCC-lines harbor potential CSC, characterized by ALDH1 and stemness marker TF expression as well as properties like invasiveness, quiescence, and EMT. CSC can be enriched by anchorage-independent culture techniques, which may be important for the investigation of their contribution to therapy resistance, tumor recurrence and metastasis.

Dataset Information

Immune phenotypes of prostate cancer cells: Evidence of epithelial immune cell-like transition?

Publications

Immune phenotypes of prostate cancer cells: Evidence of epithelial immune cell-like transition?

Similar Datasets

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