Differential expression of novel immune checkpoint receptors on tumor-infiltrating lymphocytes in patients with locally advanced breast cancer after neoadjuvant chemotherapy

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Abbasov A., Aktas Cetin E., Cabioglu N., Mollavelioglu B., Onder S., Emiroglu S., ...More

NEOPLASMA, vol.68, no.5, pp.1079-1090, 2021 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 68 Issue: 5
  • Publication Date: 2021
  • Doi Number: 10.4149/neo_2021_210127n141
  • Journal Name: NEOPLASMA
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, EMBASE, MEDLINE
  • Page Numbers: pp.1079-1090
  • Keywords: locally advanced breast cancer, PD-1, TIGIT, CTLA-4, LAG-3, TIM-3, PD-L1, ASSOCIATION, LIGAND, TIM-3
  • Istanbul University Affiliated: Yes


Immune checkpoint receptors (ICRs) were recently found to modulate the anti-tumoral immune response. This study aimed to determine the clinical and pathological associations of ICRs expression on tumor-infiltrating lymphocytes (TILs) in patients with locally advanced breast cancer (LABC) treated with neoadjuvant chemotherapy (NAC). Expressions of ICRs including PD-1, LAG-3, TIM-3, TIGIT, and CTLA-4 on CD8(+) T lymphocytes and Natural Killer (NK) cells on TILs were analyzed by flow cytometry. Patients <50 years were more likely to express CTLA-4 on CD8+ T lymphocytes compared to those >= 50 years (p=0.004). In addition, patients with ypT3-4 tumors were more likely to have increased LAG-3 expression on CD16-CD56bright NK cells (p=0.042) and PD-1 (p=0.014) and CTLA-4 (p=0.018) expressions on CD8(+) T cells in regard to those with ypT1-T2, respectively. Contrarily, PD-1 expression on CD16-CD56(bright) NK cells was found to be decreased in patients with ypN+ compared to those with ypN- (p=0.022). Furthermore, patients with HER2+ tumors were more likely to have increased TIM-3 expression on CD8(+) T cells (p=0.043), whereas patients with a better response to NAC were more likely to express TIGIT on CD8(+) T (p=0.014) and CD16-CD56(bright) NK cells (p=0.003), respectively. The new generation ICRs, TIM-3, LAG-3, and TIGIT are highly expressed in LABC following NAC in patients with poor prognostic factors. Therefore, new evolving therapies using inhibitory mAbs directed to TIM-3, LAG-3, and TIGIT could be also be considered in locally advanced breast cancers expressing these ICRs.