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RESEARCH ARTICLE Open AccessA comparison of the local immune statusbetween the primary and metastatic tumorin colorectal cancer: a retrospective studyMasatsune Shibutani * , Kiyoshi Maeda, Hisashi Nagahara, Tatsunari Fukuoka, Shinji Matsutani, Shinichiro Kashiwagi,Hiroaki Tanaka, Kosei Hirakawa and Masaichi OhiraAbstractBackground: The anticancer immune response has been reported to correlate with cancer progression. Tumor-infiltrating lymphocytes (TILs), which are one of the indicators of host immunity, affect the tumor growth,metastasis and chemoresistance. Both TILs in the primary tumor and those in the metastatic tumor have beenreported to be a useful predictor of the survival and therapeutic outcome. However, the correlation between thedensity of TILs in the primary and metastatic tumor is unclear. The aim of this study was to elucidate the correlationbetween the density of TILs in the primary and metastatic tumor.Methods: A total of 24 patients with stage IV colorectal cancer who underwent concurrent resection of the primarytumor and liver metastasis were enrolled in order to assess the correlation between the density of TILs in theprimary tumor and that in the metastatic tumor. Hematoxylin and eosin (HE)-stained tumor sections were used forthe evaluation of TILs. The density of TILs was assessed by the measurement of the area occupied by mononuclearinflammatory cells over the total stromal area at the invasive margin. In addition, to evaluate TIL subsets and theactivation/suppression status of the lymphocytes, immunohistochemistry for CD4, CD8, Forkhead boxprotein P3(FOXP3), programmed cell death 1 (PD-1), cytotoxic T-lymphocyte-associated protein 4 (CTLA4), inducible T-cell co-stimulator (ICOS), Glucocorticoid induced tumor necrosis factor receptor related protein (GITR), Human LeukocyteAntigen - antigen D Related (HLA-DR) and Granzyme B was performed, and the number of immunoreactivelymphocytes was counted.Results: According to the evaluation using the HE-stained sections, the density of tumor-infiltrating mononuclearinflammatory cells in the primary tumor was significantly associated with that in the metastatic tumor. In addition,according to the immunohistochemistry evaluation, the density of CD4 + , CD8 + and FOXP3 + TILs in the primarytumor and that in the metastatic tumor were significantly correlated with that in the metastatic tumor.Furthermore, the activation/suppression marker values of the lymphocytes (i.e., such as PD-1, ICOS, Granzyme B andthe PD-1/CD8 ratio) in the primary tumor were correlated with values in the metastatic tumor.Conclusions: The local immune status of the primary tumor was revealed to be similar to that of the metastatictumor. This suggests that the evaluation of the local immunity of the primary tumor may be a substitute for theevaluation of the local immunity of the metastatic lesion. Therefore, information on the primary tumor may beuseful when considering treatment strategies for metastatic lesions.Keywords: Colorectal cancer, Tumor-infiltrating lymphocyte, Primary tumor, Metastatic tumor* Correspondence: fbxbj429@ybb.ne.jpDepartment of Surgical Oncology, Osaka City University Graduate School ofMedicine, 1–4–3 Asahi-machi Abeno–ku, Osaka City, Osaka Prefecture545-8585, Japan© The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, andreproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link tothe Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Shibutani et al. BMC Cancer (2018) 18:371 https://doi.org/10.1186/s12885-018-4276-y