Programmed death ligand 1-positive immune cells in primary tumor or metastatic axillary lymph nodes can predict prognosis of triple-negative breast cancer even when present at < 1% in the tumor region

BACKGROUND: The efficacy of pre-operative systemic treatment (PST) combined with immune checkpoint inhibition (ICI) for triple-negative breast cancer (TNBC) has been recognized recently as being independent of the degree of programmed death ligand-1 (PD-L1) positivity of infiltrating immune cells, especially for patients with axillary lymph node metastasis (ALNM). METHODS: TNBC patients with ALNM were treated surgically between 2002 and 2016 in our facility (n = 109), of whom 38 received PST before resection. The presence of tumor-infiltrating lymphocytes (TILs) expressing CD3, CD8, CD68, PD-L1 (detected by antibody SP142) and FOXP3 at primary and metastatic LN sites was quantified. RESULTS: The size of invasive tumor and the number of metastatic axillary LN were confirmed as prognostic markers. The numbers of both CD8+ and FOXP3+ TILs at primary sites were also recognized as prognostic markers, especially for overall survival (OS) (CD8, p = 0.026; FOXP3, p < 0.001). The presence of CD8+, FOXP3+ and PD-L1+ cells was better maintained in LN after PST and may contribute to improved antitumor immunity. Provided they were present as clusters of ≥ 70 positive cells, even < 1% of immune cells expressing PD-L1 at primary sites predicted a more favorable prognosis for both disease-free survival (DFS) (p = 0.004) and OS (p = 0.020). This was the case not only for 30 matched surgical patients, but also in all 71 surgical only patients (DFS: p < 0.001 and OS: p = 0.002). CONCLUSIONS: PD-L1+ , CD8+ or FOXP3+ immune cells in the tumor microenvironment (TME) at both primary and metastatic sites are significant on prognosis, which could be a clue to expect the potential for better responses to the combination of chemotherapy and ICI, especially for patients with ALNM.