Differential expression of novel immune checkpoint receptors on tumor-infiltrating lymphocytes in patients with locally advanced breast cancer after neoadjuvant chemotherapy
NEOPLASMA, sa.5, ss.1079-1090, 2021 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Basım Tarihi: 2021
- Doi Numarası: 10.4149/neo_2021_210127n141
- Dergi Adı: NEOPLASMA
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, EMBASE, MEDLINE
- Sayfa Sayıları: ss.1079-1090
- Anahtar Kelimeler: locally advanced breast cancer, PD-1, TIGIT, CTLA-4, LAG-3, TIM-3, PD-L1, ASSOCIATION, LIGAND, TIM-3
- Açık Arşiv Koleksiyonu: AVESİS Açık Erişim Koleksiyonu
- İstanbul Üniversitesi Adresli: Evet
Özet
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.