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Tumour-infiltrating lymphocytes are correlated with higher expression levels of PD-1 and PD-L1 in early breast cancer
  1. Atsuko Kitano1,
  2. Makiko Ono1,2,
  3. Masayuki Yoshida3,
  4. Emi Noguchi1,
  5. Akihiko Shimomura1,
  6. Tatsunori Shimoi1,
  7. Makoto Kodaira1,
  8. Mayu Yunokawa1,
  9. Kan Yonemori1,
  10. Chikako Shimizu1,
  11. Takayuki Kinoshita4,
  12. Yasuhiro Fujiwara1,
  13. Hitoshi Tsuda5,
  14. Kenji Tamura1
  1. 1 Department of Breast and Medical Oncology, National Cancer Center Hospital, Tokyo, Japan
  2. 2 Department of Medical Oncology, Cancer Institute Hospital, Tokyo, Japan
  3. 3 Division of Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo, Japan
  4. 4 Department of Breast Surgery, National Cancer Center Hospital, Tokyo, Japan
  5. 5 Department of Basic Pathology, National Defense Medical College, Saitama, Japan
  1. Correspondence to Dr Kenji Tamura; ketamura{at}ncc.go.jp

Abstract

Background The presence of tumour-infiltrating lymphocytes (TILs) is a favourable prognostic factor in patients with early breast cancer. Programmed cell death-1 (PD-1) and its ligand PD-L1 are associated with a variety of adverse features. The purpose of this study was to clarify the relationships between TILs, PD-1 and PD-L1 as well as their prognostic implications in early breast cancer.

Methods We investigated 180 patients with breast cancer who received neoadjuvant chemotherapy and underwent subsequent surgery for stage II–III invasive breast carcinoma between 1999 and 2007. TIL expression was classified as low or high using a previously reported scoring model. PD-1 and PD-L1 expression levels were determined by immunohistochemistry. The correlation between PD-1 expression in TILs and PD-L1 expression in cancer cells was also investigated.

Results Higher tumour grade was significantly correlated with PD-L1 expression in tumours (p<0.0001). PD-1 and PD-L1 expression levels were associated with tumour subtype and were highest in triple-negative tumours (p<0.0001). Furthermore, expression of each of PD-1 and PD-L1 was significantly correlated with higher TIL expression and pathological complete response (pCR) (p<0.0001). PD-L1 expression in cancer cells was significantly correlated with PD-1 expression in TILs (p=0.03). The correlations between pCR and expression of each of PD-L1 and PD-1 were not significant.

Conclusion Expression of PD-L1 and PD-1 in early breast cancer is associated with higher TIL scores and pCR; conversely, expression of these proteins correlates with poor prognostic clinicopathological factors such as tumour grade and subtype. TILs, PD-1 and PD-L1 can potentially predict the response to treatment.

  • breast cancer
  • tumor-infiltrating lymphocytes
  • PD-L1
  • PD-1

This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/

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Footnotes

  • Funding This study was supported by Japan and National Cancer Center Research and Development Funds (26-A-8).

  • Competing interests None declared.

  • Ethics approval This article does not contain any studies with animals performed by any of the authors. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

  • Provenance and peer review Not commissioned; internally peer reviewed

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