Research Papers:

Immunoscore encompassing CD3+ and CD8+ T cell densities in distant metastasis is a robust prognostic marker for advanced colorectal cancer

Yoonjin Kwak _, Jiwon Koh, Duck Woo Kim, Sung Bum Kang, Woo Ho Kim and Hye Seung Lee

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Oncotarget. 2016; 7:81778-81790. https://doi.org/10.18632/oncotarget.13207

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Yoonjin Kwak1,2, Jiwon Koh2, Duck-Woo Kim3, Sung-Bum Kang3, Woo Ho Kim2, Hye Seung Lee1,2

1Department of Pathology, Seoul National University Bundang Hospital, Seongnam, South Korea

2Department of Pathology, Seoul National University College of Medicine, Seoul, South Korea

3Department of Surgery, Seoul National University Bundang Hospital, Seongnam, South Korea

Correspondence to:

Hye Seung Lee, email: [email protected]

Keywords: colorectal cancer, tumor-infiltrating lymphocytes, tumor-associated macrophage, immunoscore

Received: May 27, 2016     Accepted: October 28, 2016     Published: November 08, 2016


Background: The immunoscore (IS), an index based on the density of CD3+ and CD8+ tumor-infiltrating lymphocytes (TILs) in the tumor center (CT) and invasive margin (IM), has gained considerable attention as a prognostic marker. Tumor-associated macrophages (TAMs) have also been reported to have prognostic value. However, its clinical significance has not been fully clarified in patients with advanced CRC who present with distant metastases.

Methods: The density of CD3+, CD4+, CD8+, FOXP3+, CD68+, and CD163+ immune cells within CRC tissue procured from three sites–the primary CT, IM, and distant metastasis (DM)–was determined using immunohistochemistry and digital image analyzer (n=196). The IS was obtained by quantifying the densities of CD3+ and CD8+ TILs in the CT and IM. IS-metastatic and IS-macrophage–additional IS models designed in this study–were obtained by adding the score of CD3 and CD8 in DM and the score of CD163 in primary tumors (CT and IM), respectively, to the IS.

Result: Higher IS, IS-metastatic, and IS-macrophage values were significantly correlated with better prognosis (p=0.020, p≤0.001, and p=0.005, respectively). Multivariate analysis revealed that only IS-metastatic was an independent prognostic marker (p=0.012). No significant correlation was observed between KRAS mutation and three IS models. However, in the subgroup analysis, IS-metastatic showed a prognostic association regardless of the KRAS mutational status.

Conclusion: IS is a reproducible method for predicting the survival of patients with advanced CRC. Additionally, an IS including the CD3+ and CD8+ TIL densities at DM could be a strong prognostic marker for advanced CRC.

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