Background Tumour-infiltrating lymphocytes (TILs) can be used to monitor the immune tumour microenvironment (iTME) and predict treatment response and outcome in breast cancer. We evaluated the prognostic significance of the levels of CD8+ TILs and forkhead box protein (FOXP3)-positive TILs before and after neoadjuvant chemotherapy (NAC).
Patients and methods We examined 136 patients with breast cancer treated with NAC. The number of CD8+ TILs and FOXP3+ TILs in biopsy specimens and residual tumours was evaluated by immunohistochemistry.
Results Patients with a high rate of change in the CD8/FOXP3 ratio (CFR) had significantly better recurrence-free survival (RFS) (p<0.001, log-rank). In multivariate analysis, the rates of change in the CD8+ TIL levels and the CFR were independent predictors for RFS (HR=2.304, p=0.036 and HR=4.663, p<0.001). In patients with triple-negative and hormone receptor-positive breast cancer, the rate of change in the CFR was an independent predictor for RFS (HR=13.021, p=0.002 and HR=4.377, p=0.003).
Conclusion Improvement in the iTME following NAC is correlated with good outcome. The rate of change in the CFR may be a useful biomarker to predict prognosis of patients treated with NAC.
- tumour microenvironment
- breast cancer
- immune response
- neoadjuvant chemotherapy
- tumour-infiltrating lymphocytes
This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.
Statistics from Altmetric.com
Contributors All authors were involved in the preparation of the manuscript. WG collected the data and wrote the manuscript. SK, YA, KTakad, KTakah, TH and TT performed the operation and designed the study. WG, SK and ST summarised the data and revised the manuscript. MOhs performed the pathological diagnosis. HM, KH and MOhi made substantial contribution to the study design, performed the operation and revised the manuscript. All authors read and approved the final manuscript.
Funding This study was supported in part by Grants-in Aid for Scientific Research (KAKENHI, nos 25461992, 26461957 and 17K10559) from the Ministry of Education, Science, Sports, Culture and Technology of Japan.
Competing interests Not declared.
Patient consent Obtained.
Ethics approval The Ethics Committee of Osaka City University approved the study protocol (no 926).
Provenance and peer review Not commissioned; externally peer reviewed.
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.