Abstract 4144: The prognostic value of tumor-infiltrating immune cells and clinical application of immunoscoring methods in advanced colorectal carcinoma
Authors: Kwak Yoonjin , Kim Duck Woo , Kang Sung Bum , Kim Woo Ho , Lee Hye Seung 
Published: July 2016

Background Immunoscore(IS) which quantifies tumor-infiltrating lymphocyte (TIL) has been noteworthy for novel prognostic biomarker especially in colorectal cancer (CRC). Recent studies have been insisted that IS method is superior to current tumor-node-metastases staging system in various cancers. The prognostic significance of tumor-associate macrophage (TAM) also has been suggested. However, studies in the past included patients with stage I-III CRCs and the clinical implication of TIL and TAM has not been fully clarified in advance CRC patients who presented distant metastases. In this study, we investigated TIL and TAM in the primary site and the corresponding metastatic organ to identified the heterogeneity of each characteristics according to tumor location. We evaluated the prognostic significance of TIL and TAM in advanced CRCs. Also we designed new IS methods and conducted comparative analysis between existing and new methods for prognostic predictive value. Methods. Using immunohistochemistry and digital image analyzer, we measured the density of CD3, CD4, CD8 and FOXP3-positive lymphocyte of 196 advanced CRC patients. CD68 and CD163 immunohistochemistry was conducted to evaluate the density of tumor-associated macrophage. These properties were examined within tissue from four sites (the center (CT) and periphery of the primary cancer (IM), a distant metastasis (DM) and a lymph node metastasis (LM)). High density of lymphocyte marker and low density of macrophage marker in each region recorded as a score. IS method is based on the combination of two markers (CD3 and CD8) in two regions (CT and IM). Newly designed model, IS-metastatic and IS-macrophage included the additional scores of two markers (CD3 and CD8) in DM and macrophage markers (CD68 and CD163) in CT, respectively. Results. The each density of TIL and TAM showed significant heterogeneity according to the tumor location. Patients with high density of CD3-positive lymphocyte in CT presented favorable outcome (p = 0.030). In contrast, patients showing high density of CD68 and CD163-positive macrophage in CT had significantly worse prognosis (p = 0.011 and p&lt;0.001, respectively). Higher IS (score 3-4) was significantly correlated with better survival rate (p = 0.020). Patients with higher IS-metastatic as well as IS-macrophage (score 4-6) also showed significantly better outcome (p = &lt;0.001 and p = 0.005, respectively). In multivariate analysis, IS-Metastatic model was independent prognostic factor (p = 0.012). Conclusions. TIL and TAM are distributed heterogeneously with respect to the tumor location in CRC patients and has a significant effect on patients outcome. IS is reproducible methods and applicable for predicting survival in advanced CRC. New IS model including CD3- and CD8-positive cells at distant metastasis could be an independent prognostic biomarker in advanced CRC patients.

Citation Format: Yoonjin Kwak, Duck Woo Kim, Sung Bum Kang, Woo Ho Kim, Hye Seung Lee. The prognostic value of tumor-infiltrating immune cells and clinical application of immunoscoring methods in advanced colorectal carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4144.