Impact of adjuvant chemotherapy and radiotherapy on tumour-infiltrating lymphocytes and PD-L1 expression in metastatic breast cancer

Br J Cancer. 2023 Feb;128(4):568-575. doi: 10.1038/s41416-022-02072-2. Epub 2022 Dec 15.

Abstract

Background: Chemotherapy and radiotherapy were postulated to induce an inflamed tumour microenvironment. We aimed to evaluate the effects of adjuvant chemotherapy/radiotherapy on tumour-infiltrating lymphocytes (TILs) and programmed death-ligand 1 (PD-L1) expression in metastatic breast cancer.

Methods: We identified paired primary and metastatic tumours in 85 patients with breast cancer. Stromal TILs were assessed according to international guidelines. PD-L1 expression was evaluated using the VENTANA SP142 assay.

Results: TILs were significantly lower in metastatic tumours than in primary tumours (12.2 vs. 8.3%, p = 0.049). PD-L1 positivity was similar between primary and metastatic tumours (21.2 vs. 14.1%, p = 0.23). TILs were significantly lower in patients who received adjuvant chemotherapy than in those who did not (-9.07 vs. 1.19%, p = 0.01). However, radiotherapy had no significant effect on TILs (p = 0.44). Decreased TILs predicted worse post-recurrence survival (hazard ratio, 2.94; 95% confidence interval [CI]: 1.41-6.13, p = 0.003), while increased TILs was associated with a better prognosis (HR, 0.12; 95% CI: 0.02-0.08, p = 0.04).

Conclusions: TILs decreased in metastatic tumours, particularly in patients who relapsed after adjuvant chemotherapy. Changes in TILs from primary to metastatic sites could be a prognostic factor after recurrence.

MeSH terms

  • B7-H1 Antigen / metabolism
  • Breast Neoplasms* / pathology
  • Chemotherapy, Adjuvant
  • Female
  • Humans
  • Lymphocytes, Tumor-Infiltrating / pathology
  • Prognosis
  • Tumor Microenvironment

Substances

  • CD274 protein, human
  • B7-H1 Antigen