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Cancer Immunology, Immunotherapy

, Volume 68, Issue 4, pp 563–575 | Cite as

Prognostic value of tumour-infiltrating CD8+ lymphocytes in rectal cancer after neoadjuvant chemoradiation: is indoleamine-2,3-dioxygenase (IDO1) a friend or foe?

  • Julia Schollbach
  • Stefan Kircher
  • Armin Wiegering
  • Florian Seyfried
  • Ingo Klein
  • Andreas Rosenwald
  • Christoph-Thomas Germer
  • Stefan LöbEmail author
Original Article
  • 194 Downloads

Abstract

The prognostic value of the local immune phenotype in patients with colorectal cancer has been extensively studied. Neoadjuvant radiotherapy and/or chemotherapy may potentially influence these immune responses. In this study, we examined the prognostic role of indoleamine-2,3-Dioxygenase (IDO1) and infiltrating cytotoxic T lymphocytes (CD8+) in locally advanced rectal carcinomas after neoadjuvant treatment. Expression of IDO1 and CD8 was evaluated by immunohistochemistry in 106 archival tumour tissue samples from patients following neoadjuvant chemoradiation and radical resection. The average infiltration of IDO1+ and CD8+ cells was calculated along the tumour invasive front, in the tumour centre and within the neoplastic cells and expressed as total scores. Of the tumour specimens evaluable for immunohistochemistry, 100% showed CD8+ lymphocyte infiltration and 93.4% stained positive for IDO1. Total IDO1 score positively correlated with total CD8 score for all three subsites (p = 0.002, Kendall-tau-b 0.357). A high total CD8 score was positively correlated with lower ypUICC-stages (p = 0.047) and lower ypT-categories (p = 0.032). Total IDO1 expression showed a clear trend towards a lower risk of recurrence (p = 0.078). A high total IDO1 score was an independent prognostic marker for prolonged disease-free survival (HR 0.38, p = 0.046) and a high total CD8 score for favourable overall survival (HR 0.16, p = 0.029). Analysis of the local CD8 and IDO1 expression profile may be a helpful tool in predicting prognosis for patients with locally advanced rectal cancer following neoadjuvant chemoradiation.

Keywords

Rectal cancer Neoadjuvant therapy IDO1 Tumour-infiltrating lymphocytes Survival Prognostic factors 

Abbreviations

AJCC/UICC

American Joint Committee on Cancer/Union Internationale Contre le Cancer

CD8

Cytotoxic T lymphocyte

DFS

Disease-free survival

HR

Hazard ratio

IDO1

Indoleamine-2,3-Dioxygenase 1

IE

Intraepithelial

LARC

Locally advanced rectal cancer

OS

Overall survival

ST

Stromal

TDO

Tryptophan-2,3-dioxygenase

TME

Total mesorectal excision

TNM

Tumour-node-metastasis

Notes

Acknowledgements

The authors would like to thank Sabine Roth for her tireless efforts and qualified support in the set-up of IDO1 immunohistochemistry. We thank Mohammed Hankir for proofreading the manuscript.

Author contributions

Julia Schollbach: performed immunohistochemistry, manuscript writing. Stefan Kircher: performed immunohistochemistry. Armin Wiegering: study design, manuscript writing. Florian Seyfried: study design, manuscript writing. Ingo Klein: study design. Andreas Rosenwald: study design. Christoph-Thomas Germer: manuscript writing. Stefan Löb: study design, manuscript writing.

Funding

No relevant funding.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

Patient and treatment characteristics were retrospectively collected from patient records and the Würzburg comprehensive cancer registry. All procedures performed were in accordance with the standards of the institutional ethical committee and with the 1964 Helsinki declaration and its later amendments. Approval of the study was obtained from the Ethics Committee, Medical Faculty, University of Würzburg, Germany (reference number 34/16). All patients provided informed written consent to the use of their anonymized data in scientific studies.

Supplementary material

262_2019_2306_MOESM1_ESM.pdf (161 kb)
Supplementary material 1 (PDF 161 KB)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of General-, Visceral-, Transplant-, Vascular- and Paediatric SurgeryUniversity Hospital of WürzburgWürzburgGermany
  2. 2.Department of PathologyUniversity of WürzburgWürzburgGermany
  3. 3.Theodor Boveri Institute, BiocenterUniversity of WürzburgWürzburgGermany
  4. 4.Comprehensive Cancer Center MainfrankenUniversity of WürzburgWürzburgGermany

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