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Image analyzer-based assessment of tumor-infiltrating T cell subsets and their prognostic values in colorectal carcinomas.

ABSTRACT: To find useful tools to evaluate the prognosis in colorectal carcinoma (CRC) patients, we investigated the prognostic values of tumor-infiltrating T lymphocyte subsets according to intratumoral subsites as well as clinical or molecular characteristics. Immunohistochemistry for CD8, CD45RO, and FOXP3 was performed, and densities of the T cell subsets in each tissue microarray core (cells/mm2) were measured by image analysis. In the training set (n = 218) of CRC, T cell subset densities in the invasion front were more strongly associated with patient outcome than those in the tumor center. In the validation set (n = 549), T cell subset densities in the invasion front were evaluated. Univariate analysis showed that all three T cell subset densities were significantly associated with longer progression free survival and overall survival time (p < 0.001). In multivariate analysis, a high CD45RO density correlated independently with longer progression free survival (p = 0.011) and overall survival time (p = 0.007) in CRC patients, regardless of tumor location or adjuvant chemotherapy status. Our results showed that CD45RO density in the invasion front was the only independent prognostic factor regarding CRC. However, CD8 and FOXP3 densities were also independent prognostic factors in certain clinical settings. Thus, image analysis of tissue microarray cores in the invasion front of CRC could be used as a valid method for evaluating the prognostic significance of T cell subset densities.

SUBMITTER: Kim Y

PROVIDER: S-EPMC4398542 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Image analyzer-based assessment of tumor-infiltrating T cell subsets and their prognostic values in colorectal carcinomas.

Kim Younghoon Y Bae Jeong Mo JM Li Gang G Cho Nam Yun NY Kang Gyeong Hoon GH

PloS one 20150415 4

To find useful tools to evaluate the prognosis in colorectal carcinoma (CRC) patients, we investigated the prognostic values of tumor-infiltrating T lymphocyte subsets according to intratumoral subsites as well as clinical or molecular characteristics. Immunohistochemistry for CD8, CD45RO, and FOXP3 was performed, and densities of the T cell subsets in each tissue microarray core (cells/mm2) were measured by image analysis. In the training set (n = 218) of CRC, T cell subset densities in the inv ...[more]

PMID: 25875774

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Project description:Tumor-infiltrating leukocytes (TILs) are immune cells surrounding tumor cells, and several studies have shown that TILs are potential survival predictors in different cancers. However, few studies have dissected the differences between hepatitis B- and hepatitis C-related hepatocellular carcinoma (HBV-HCC and HCV-HCC). Therefore, we aimed to determine whether the abundance and composition of TILs are potential predictors for survival outcomes in HCC and which TILs are the most significant predictors. Two bioinformatics algorithms, ESTIMATE and CIBERSORT, were utilized to analyze the gene expression profiles from 6 datasets, from which the abundance of corresponding TILs was inferred. The ESTIMATE algorithm examined the overall abundance of TILs, whereas the CIBERSORT algorithm reported the relative abundance of 22 different TILs. Both HBV-HCC and HCV-HCC were analyzed. The results indicated that the total abundance of TILs was higher in non-tumor tissue regardless of the HCC type. Alternatively, the specific TILs associated with overall survival (OS) and recurrence-free survival (RFS) varied between subtypes. For example, in HBV-HCC, plasma cells (hazard ratio [HR] = 1.05; 95% CI 1.00-1.10; p = 0.034) and activated dendritic cells (HR = 1.08; 95% CI 1.01-1.17; p = 0.03) were significantly associated with OS, whereas in HCV-HCC, monocytes (HR = 1.21) were significantly associated with OS. Furthermore, for RFS, CD8+ T cells (HR = 0.98) and M0 macrophages (HR = 1.02) were potential biomarkers in HBV-HCC, whereas neutrophils (HR = 1.01) were an independent predictor in HCV-HCC. Lastly, in both HBV-HCC and HCV-HCC, CD8+ T cells (HR = 0.97) and activated dendritic cells (HR = 1.09) had a significant association with OS, while γ delta T cells (HR = 1.04), monocytes (HR = 1.05), M0 macrophages (HR = 1.04), M1 macrophages (HR = 1.02), and activated dendritic cells (HR = 1.15) were highly associated with RFS. Conclusions: These findings demonstrated that TILs are potential survival predictors in HCC and different kinds of TILs are observed according to the virus type. Therefore, further investigations are warranted to elucidate the role of TILs in HCC, which may improve immunotherapy outcomes.

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Dataset Information

Image analyzer-based assessment of tumor-infiltrating T cell subsets and their prognostic values in colorectal carcinomas.

Publications

Image analyzer-based assessment of tumor-infiltrating T cell subsets and their prognostic values in colorectal carcinomas.

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