Annals of Surgical Oncology

, Volume 21, Supplement 3, pp 414–421 | Cite as

CD8+ and FOXP3+ Tumor-Infiltrating T Cells Before and After Chemoradiotherapy for Rectal Cancer

  • Eiji ShintoEmail author
  • Kazuo Hase
  • Yojiro Hashiguchi
  • Akinori Sekizawa
  • Hideki Ueno
  • Atsushi Shikina
  • Yoshiki Kajiwara
  • Hirotoshi Kobayashi
  • Megumi Ishiguro
  • Junji Yamamoto
Colorectal Cancer



CD8+ cytotoxic T cells and forkhead box P3 (FOXP3)+ regulatory T cells are major players in tumor immunity. Increased CD8+ tumor-infiltrating lymphocytes (TILs) and high CD8/FOXP3 TIL ratios are associated with improved survival. Neoadjuvant chemoradiotherapy (CRT) can result in tumor regression; however, immunomodulation during CRT for rectal cancer has not been thoroughly assessed. We investigated whether neoadjuvant CRT altered the in situ immune cell population and clinical implications of TIL accumulation before and after CRT.


We recruited 93 rectal cancer patients who underwent neoadjuvant CRT and radical resection. Pretreatment biopsy and post-CRT resected specimens were immunostained for CD8 and FOXP3, and the densities of stromal (STL) and intraepithelial (IEL) immunopositive TILs were determined separately. In addition, 54 patients with resections but without neoadjuvant CRT were enrolled for comparison.


CD8+ STL density doubled after CRT (average counts: 92 vs. 230 per microscopic field using a 20 × objective lens; P < 0.0001), whereas FOXP3+ STL counts remained stable (109 vs. 109). Compared with non-CRT cases, CRT increased CD8+ STL density. Multivariate analyses demonstrated that high post-CRT CD8 + STL density was associated with better prognosis (5-year recurrence-free survival: 87.5 vs. 57.8 %; P = 0.0058) and that a high pretreatment CD8/FOXP3 IEL ratio was a predictor of favorable tumor regression (P = 0.0029).


Favorable anticancer immunity occurred after CRT for rectal cancer by altering TIL subsets. A high CD8/FOXP3 IEL ratio before CRT and a high CD8+ STL density after CRT were associated with a favorable clinical outcome.


Rectal Cancer Resected Specimen Total Mesorectal Excision Rectal Cancer Patient Lower Rectal Cancer 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This work was supported in part by the National Cancer Center Research and Development Fund (23-A-11 and 23-A-26) and by Japan Society for the Promotion of Science KAKENHI (23501302 and 25462074). We certify that we do not have any commercial associations that may pose a conflict of interest in connection with this article.


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Copyright information

© Society of Surgical Oncology 2014

Authors and Affiliations

  • Eiji Shinto
    • 1
    Email author
  • Kazuo Hase
    • 1
  • Yojiro Hashiguchi
    • 2
  • Akinori Sekizawa
    • 1
  • Hideki Ueno
    • 1
  • Atsushi Shikina
    • 1
  • Yoshiki Kajiwara
    • 1
  • Hirotoshi Kobayashi
    • 3
  • Megumi Ishiguro
    • 3
  • Junji Yamamoto
    • 1
  1. 1.Department of SurgeryNational Defense Medical CollegeSaitamaJapan
  2. 2.Department of SurgeryTeikyo UniversityTokyoJapan
  3. 3.Department of Surgical Oncology, Graduate SchoolTokyo Medical and Dental UniversityTokyoJapan

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