Iranian journal of immunology : IJI · 2025
Expression and Prognostic Significance of PD-1/PD-Ls in Breast Cancer Draining Lymph Nodes.
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Mansourabadi Zahra, Moazzeni Ali, Akrami Majid, Fakhimi Maryam, Faghih Zahra
Аннотация
BACKGROUND: Tumor-draining lymph nodes play a pivotal role in orchestrating immune cell trafficking and initiating antitumor responses. Among immunoregulatory molecules, programmed cell death protein 1 (PD-1) has emerged as a central mediator in tumor-induced immunosuppression.
OBJECTIVE: To investigate the expression patterns of PD-1 and its ligands (PD-L1, PD-L2) in the tumor-draining lymph nodes of patients with breast cancer (BC).
METHODS: Lymph node samples were freshly collected from BC patients undergoing surgery. Mononuclear cells were isolated and analyzed by flow cytometry for surface markers CD45, PD-1, PD-L1, and PD-L2. Data were analyzed using FlowJo v10.8.1.
RESULTS: PD-1 was detected on 9.48 ± 5.19% of CD45+ cells, whereas PD-L1 and PD-L2 were expressed at lower levels (1.73 ± 0.85% and 1.68 ± 0.84%, respectively). Despite a significant reduction in the percentage of CD45+ lymphocytes, the frequencies of PD-1+ and PD-L2+ subsets were significantly elevated in patients with poorly-differentiated and advanced-stage tumors (P<0.05). Additionally, the frequency of PD-1+ lymphocytes was significantly higher in patients with the triple-negative tumors (P=0.014) and in those negative for estrogen and progesterone receptor (P=0.001).
CONCLUSION: Elevated expression of PD-1 and its ligands in BC-draining lymph nodes is associated with adverse clinical features, suggesting their role in immune evasion. These findings along with higher frequency of PD-1+ lymphocyte in triple-negative patients may inform subtype-specific therapeutic strategies and predict responsiveness to PD-1/PD-Ls blockade therapies. Future studies should include functional analyses with broader immunophenotyping to further elucidate these mechanisms.
OBJECTIVE: To investigate the expression patterns of PD-1 and its ligands (PD-L1, PD-L2) in the tumor-draining lymph nodes of patients with breast cancer (BC).
METHODS: Lymph node samples were freshly collected from BC patients undergoing surgery. Mononuclear cells were isolated and analyzed by flow cytometry for surface markers CD45, PD-1, PD-L1, and PD-L2. Data were analyzed using FlowJo v10.8.1.
RESULTS: PD-1 was detected on 9.48 ± 5.19% of CD45+ cells, whereas PD-L1 and PD-L2 were expressed at lower levels (1.73 ± 0.85% and 1.68 ± 0.84%, respectively). Despite a significant reduction in the percentage of CD45+ lymphocytes, the frequencies of PD-1+ and PD-L2+ subsets were significantly elevated in patients with poorly-differentiated and advanced-stage tumors (P<0.05). Additionally, the frequency of PD-1+ lymphocytes was significantly higher in patients with the triple-negative tumors (P=0.014) and in those negative for estrogen and progesterone receptor (P=0.001).
CONCLUSION: Elevated expression of PD-1 and its ligands in BC-draining lymph nodes is associated with adverse clinical features, suggesting their role in immune evasion. These findings along with higher frequency of PD-1+ lymphocyte in triple-negative patients may inform subtype-specific therapeutic strategies and predict responsiveness to PD-1/PD-Ls blockade therapies. Future studies should include functional analyses with broader immunophenotyping to further elucidate these mechanisms.