Abstract 635: CD8+ tumor-infiltrating T cells before and after neoadjuvant therapy correlates with the pathological response in rectal cancer
Authors: Matsutani Shinji , Shibutani Masatsune , Maeda Kiyoshi , Nagahara Hisashi , Fukuoka Tatsunari , Amano Ryosuke , Tanaka Hiroaki , Muguruma Kazuya , Hirakawa Kosei , Ohira Masaichi 
Published: July 2017

Abstract
Background: Recently, neoadjuvant therapy (ie. neoadjuvant chemotherapy, neoadjuvant chemoradiationtherapy) for locally advanced rectal cancer has been generally performed. Although in unresponsive cases it may have disadvantages such as tumor progression or delaying surgery, factors predicting the clinical response to neoadjuvant therapy have not been adequately defined. Meanwhile CD8+ Tumor-infiltrating lymphocytes (TILs) have been reported to have a crucial effect in tumor progression and outcome as primary host immune response in various types of cancer, and antitumor immune effect has been reported to contribute to the response to radiotherapy and chemotherapy. The aim of this study was to elucidate the correlation between the local immune status and the effectiveness of the neoadjuvant therapy for locally advanced rectal cancer.
Patients and methods: A total of 51 patients who underwent curative operation for locally advanced rectal cancer after neoadjuvant therapy were enrolled. We retrospectively examined the number of CD8+ tumor-infiltrating lymphocytes (TILs) using immunohistochemical staining of pretreatment biopsy samples and resected specimens, and assessed the correlation with pathological response. The grade of tumor response was evaluated according to the definitions in the Japanese Classification of Colorectal Carcinoma. Grade0-1a were defined as “poor response” and Grade1b-3 were defined as “good response”. We set each median value of the number of CD8+ TILs as the cut-off value.
Results: For the 26 patients with pretreatment biopsy samples, we classified the the patients into the poor response group (n=14) and the good response group (n=12). Then we set 6.0 as the cut-off value and classified the patients into the high pretreatment CD8+ TILs group (n=14) and the low pretreatment CD8+ TILs group(n=12). Low pretreatment CD8+ TILs were associated with poor response to neoadjuvant therapy (p=0.036). For resected samples (n=51), we classified the patients into the poor response group (n=25) and the good response group (n=26). Then we set 10.8 as the cut-off value and classified the patients into the high posttreatment CD8+ TILs group (n=28) and the low posttreatment CD8+ TILs group(n=23). Low posttreatment CD8+ TILs were also associated with poor response to neoadjuvant therapy (p&lt;0.001). Additionally, the number of pretreatment CD8+ TILs tend to be related to the number of posttreatment CD8+ TILs.
Conclusion: In locally advanced rectal cancer patients, T lymphocyte-mediated immune reactions play an important role in tumor response to neoadjuvant therapy, and the quantitative measurement of CD8+ TILs in pretreatment biopsy samples may be a predictor of the clinical effectiveness of neoadjuvant therapy for locally advanced rectal cancer. Moreover, low posttreatment CD8+ TILs were associated with poor response to neoadjuvant therapy.
Citation Format: Shinji Matsutani, Masatsune Shibutani, Kiyoshi Maeda, Hisashi Nagahara, Tatsunari Fukuoka, Ryosuke Amano, Hiroaki Tanaka, Kazuya Muguruma, Kosei Hirakawa, Masaichi Ohira. CD8+ tumor-infiltrating T cells before and after neoadjuvant therapy correlates with the pathological response in rectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 635. doi:10.1158/1538-7445.AM2017-635