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Density of CD8+ lymphocytes in biopsy samples combined with the circulating lymphocyte ratio predicts pathologic complete response to chemoradiotherapy for rectal cancer

Authors Xiao BY, Peng JH, Zhang RX, Xu J, Wang YC, Fang YJ, Lin JZ, Pan ZZ, Wu XJ

Received 1 September 2017

Accepted for publication 12 October 2017

Published 27 November 2017 Volume 2017:9 Pages 701—708

DOI https://doi.org/10.2147/CMAR.S150622

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 2

Editor who approved publication: Dr Antonella D'Anneo


Binyi Xiao,1,* Jianhong Peng,1,* Rongxin Zhang,1,* Jing Xu,2 Yongchun Wang,2 Yujing Fang,1,2 Junzhong Lin,1 Zhizhong Pan,1 Xiaojun Wu1

1Department of Colorectal Surgery, 2Department of Experimental Research, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China

*These authors contributed equally to this work

Objectives: The systemic status and local immune status, as determined by the neutrophil–­lymphocyte ratio (NLR) or the lymphocyte ratio (LYMR) and tumor-infiltrating lymphocyte (TIL) count, respectively, have been suggested as predictors of the tumor response to neoadjuvant chemoradiotherapy (nCRT) in rectal cancer, although the utility of these measures remains controversial. We aimed to investigate the values of the LYMR, NLR and TIL count and their combinations (TIL–LYMR/TIL–NLR) in predicting pathologic complete response (pCR) after nCRT.
Patients and methods: Pretreatment biopsy samples and data from the blood tests of 92 patients with rectal cancer who underwent curative resection after nCRT were retrospectively obtained. CD8+ TILs were immunostained using an antibody against CD8. The density of CD8+ TILs was recorded as the number of CD8+ T cells per square millimeter, and the results were classified as either “high” or “low”. The LYMR and NLR were calculated using pretreatment blood test data and categorized into either “high” or “low” groups. TIL–LYMR was graded as “low,” “mid” or “high” when neither, one or both the CD8+ TIL count and LYMR were “high,” respectively. TIL–NLR was graded similarly. The associations between TILs and LYMR, NLR and their combinations (TIL–LYMR/TIL–NLR) were evaluated.
Results: pCR was significantly associated with a high LYMR, a low NLR and increased chemotherapy cycles (P=0.039, P=0.043 and P=0.015, respectively), but not with the CD8+ TIL count or carcinoembryonic antigen (CEA) level (P=0.100 and P=0.590, respectively). Additionally, 40% of patients with high LYMR and 40.7% with low NLR achieved pCR, whereas only 19.7% with low LYMR and 20.3% with high NLR did so. When the combinations were assessed, TIL–LYMR showed a positive correlation with pCR (P=0.038), while no association between TIL–NLR and pCR was found (P=0.916). In multivariate analysis, TIL–LYMR remained an independent predictor of pCR (odds ratio [OR]=1.833, 95% confidence interval [CI]=1.069–3.142, P=0.028).
Conclusion: High LYMR, low NLR and high TIL–LYMR at baseline are predictive of pCR to nCRT for patients with rectal cancer. These parameters may help identify pCR patients and provide additional information for therapeutic decision-making.

Keywords: chemoradiotherapy, rectal cancer, pathologic complete response, tumor-infiltrating lymphocytes, lymphocyte ratio, neutrophil–lymphocyte ratio

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