Document Type : Original Article
Authors
1 Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
2 Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
3 Department of Hematology, Faculty of Allied Medicine, Bushehr University of Medical Sciences, Bushehr, Iran.
4 Breast Diseases Research Center, Department of Surgical Oncology, Shiraz University of Medical Sciences, Shiraz, Iran.
5 Department of Dermatology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA
Abstract
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.
Result: 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.
Keywords
)