Abstract

PurposeNumerous reports indicate that tumor-infiltrating lymphocytes (TILs) are a prognostic factor in various cancers and that they must be good biomarkers. However, the methods of evaluating TILs differ in each study; thus, there is not yet a standardized methodology for evaluating TILs. The purpose of this study is to evaluate the prognostic significance of tumor-infiltrating lymphocytes (TILs) in patients with colorectal cancer (CRC) using the new method proposed by the International TILs Working Group in breast cancer and to standardize the method of evaluating TILs in CRC.MethodsWe retrospectively reviewed a database of 160 patients with Stage II or III CRC. The density of TILs was assessed by measuring the area occupied by mononuclear cells over the stromal area on hematoxylin and eosin (H-E)-stained sections. We set 42% as the cut-off percentage of the area occupied by TILs according to the receiver operating characteristic curve, and we classified patients into the high-TILs and the low-TILs groups.ResultsThe rates of relapse-free survival (RFS) and overall survival (OS) in the high-TILs group were significantly higher than those in the low-TILs group. A multivariate analysis showed that the density of TILs was independently associated with RFS and OS. Moreover, the density of TILs assessed by an observer was significantly associated with the density of TILs assessed by the automated imaging software program.ConclusionsThe new method for evaluating TILs, which was recommended by the International TILs Working Group in breast cancer, might be a useful predictive factor in colorectal cancer patients.

Highlights

  • Colorectal cancer (CRC) is the third most common cancer in the world [1]

  • The new method for evaluating tumor-infiltrating lymphocytes (TILs), which was recommended by the International TILs Working Group in breast cancer, might be a useful predictive factor in colorectal cancer patients

  • Tumor-infiltrating lymphocytes (TILs) are associated with the immune status of host and various reports have shown the TIL level to be a favorable biomarker in the prognosis of numerous cancers, including colorectal cancer [3,4,5,6]

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Summary

Introduction

Colorectal cancer (CRC) is the third most common cancer in the world [1]. the surgical approach and chemotherapy for CRC have improved, the prognosis remains poor, as one-third of patients who undergo curative resection die within five years after surgery [2]. In addition to tumor factors, the local tumor environment (i.e., extracellular matrix, immune cells, and cytokines) has an important role in tumor growth, invasion, metastasis and proliferation. These are considered to be prognostic factors in patients with colorectal cancer [3,4,5,6,7,8]. Tumor-infiltrating lymphocytes (TILs) are associated with the immune status of host and various reports have shown the TIL level to be a favorable biomarker in the prognosis of numerous cancers, including colorectal cancer [3,4,5,6]. The methods of evaluating TILs differ in each study; there is not yet a standardized methodology for evaluating TILs

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