Comparative analysis of PD-L1 expression and tumor-infiltrating lymphocytes between primary breast cancer and matched metastatic lesions: implications for immunotherapy

Introduction:
The PD-1/PD-L1 immune checkpoint pathway plays a critical role in tumor immune escape and disease progression. This study investigated differences in tumor-infiltrating lymphocytes (TILs) and PD-L1 expression between primary breast cancers and matched metastatic lesions, and their relationships with clinical outcomes.

Material and methods:
We retrospectively analyzed 54 female breast cancer patients who underwent radical mastectomy between May 2011 and December 2018 at the Second Affiliated Hospital of Nanchang University and later developed recurrent disease. Immunohistochemical (IHC) analysis was performed on matched primary and metastatic tumor samples to evaluate TILs and PD-L1 expression patterns. Associations between these immune parameters and clinical characteristics were assessed.

Results:
IHC analysis of 50 paired primary and metastatic lesions revealed distinct PD-L1+ TIL expression patterns across different molecular subtypes of breast cancer. Patients with PD-L1+ tumors showed significantly shorter median disease-free survival (DFS) and overall survival (OS) compared to those with PD-L1– tumors. We observed significant differences in the immune microenvironment between primary and metastatic sites, with metastatic lesions showing consistently lower TIL density, PD-L1+ TIL density, and tumor PD-L1 expression compared to matched primary tumors.

Conclusions:
Our findings demonstrate systematic differences in immune parameters between primary and metastatic breast cancer sites, with reduced immune infiltration in metastatic lesions. The data suggest that targeting the PD-1/PD-L1 pathway may be particularly beneficial in patients with PD-L1+ TIL-high primary tumors, potentially by reinvigorating anti-tumor immune responses.