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S100A8⁺ stroma cells predict a good prognosis and inhibit aggressiveness in colorectal carcinoma.

ABSTRACT: Gene microarray and bioinformatic analysis showed that S100A8 was more abundant in the stroma surrounding tumor buddings (TBs) than in the stroma surrounding primary tumor cells in colorectal carcinomas. Here, S100A8⁺ cells in 419 colorectal carcinoma samples were stained by immunohistochemistry and counted using Image-pro plus 6.0. TBs were also counted and biomarkers associated with the epithelial-mesenchymal transition and apoptosis were assessed by immunohistochemistry. We evaluated the association between S100A8⁺ cells and clinico-pathological variables as well as survival. Migration and invasion as well as biomarkers of the epithelial-mesenchymal transition and apoptosis were tested in CRC cells, treated with graded concentrations of recombinant human S100A8 protein. We found that the density of S100A8⁺ cells in the tumor invasive front (S100A8⁺_TIF) clearly distinguished patients with 5-y survival from those who did not survive (p = 0.01). The S100A8⁺-associated tumor budding (SATB) index determined by the S100A8⁺_TIF and TB was an independent predictor of overall survival (p = 0.001) other than the S100A8⁺_TIF or TB alone. Migration and invasion properties of CRC cells were inhibited by recombinant human S100A8 treatment. The particular S100A8⁺ cells in the stroma were associated with important biomarkers of the epithelial-mesenchymal transition (E-cadherin and SNAIL) and apoptosis (BCL2). In conclusion, S100A8⁺ cells in the stroma predict a good prognosis in colorectal carcinoma. An index combining S100A8⁺ cells and TB independently predicts survival. Recombinant human S100A8 inhibited CRC cell migration and invasion, which was involved in epithelial-mesenchymal transition (E-cadherin and SNAIL) and apoptosis (BCL2).

SUBMITTER: Li S

PROVIDER: S-EPMC5283617 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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S100A8+ stroma cells predict a good prognosis and inhibit aggressiveness in colorectal carcinoma.

Li Si S Xu Fangying F Li Hui H Zhang Jing J Zhong Anjing A Huang Bin B Lai Maode M

Oncoimmunology 20161212 1

Gene microarray and bioinformatic analysis showed that S100A8 was more abundant in the stroma surrounding tumor buddings (TBs) than in the stroma surrounding primary tumor cells in colorectal carcinomas. Here, S100A8+ cells in 419 colorectal carcinoma samples were stained by immunohistochemistry and counted using Image-pro plus 6.0. TBs were also counted and biomarkers associated with the epithelial-mesenchymal transition and apoptosis were assessed by immunohistochemistry. We ...[more]

PMID: 28197382

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Project description:BackgroundFunctional interactions between immune cells and neoplastic cells in the tumor immune microenvironment have been actively pursued for both biomarker discovery for patient stratification, as well as therapeutic anti-cancer targets to improve clinical outcomes. Although accumulating evidence indicates that intratumoral infiltration of immune cells has prognostic significance, limited information is available on the spatial infiltration patterns of immune cells within intratumoral regions. This study aimed to understand the intratumoral heterogeneity and spatial distribution of immune cell infiltrates associated with cell phenotypes and prognosis in head and neck squamous cell carcinoma (HNSCC).MethodsA total of 88 specimens of oropharyngeal squamous cell carcinoma, categorized into discovery (n = 38) and validation cohorts (n = 51), were analyzed for immune contexture by multiplexed immunohistochemistry (IHC) and image cytometry-based quantification. Tissue segmentation was performed according to a mathematical morphological approach using neoplastic cell IHC images to dissect intratumoral regions into tumor cell nests versus intratumoral stroma.ResultsTissue segmentation revealed heterogeneity in intratumoral T cells, varying from tumor cell nest-polarized to intratumoral stroma-polarized distributions. Leukocyte composition analysis revealed higher ratios of TH1/TH2 in tumor cell nests with higher percentages of helper T cells, B cells, and CD66b+ granulocytes within intratumoral stroma. A discovery and validation approach revealed a high density of programmed death receptor-1 (PD-1)+ helper T cells in tumor cell nests as a negative prognostic factor for short overall survival. CD163+ tumor-associated macrophages (TAM) provided the strongest correlation with PD-1+ helper T cells, and cases with a high density of PD-1+ helper T cells and CD163+ TAM had a significantly shorter overall survival than other cases.ConclusionThis study reveals the significance of analyzing intratumoral cell nests and reports that an immune microenvironment with a high density of PD-1+ helper T cells in tumoral cell nests is a poor prognostic factor for HNSCC.

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S100A8⁺ stroma cells predict a good prognosis and inhibit aggressiveness in colorectal carcinoma.

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S100A8<sup>+</sup> stroma cells predict a good prognosis and inhibit aggressiveness in colorectal carcinoma.

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