PD-L1-positive circulating endothelial progenitor cells associated with immune response to PD-1 blockade in patients
Nai-Wen Su1,2, Shuen-Han Dai3, Kate Hsu2,4,5
1Department of Hematology, MacKay Memorial Hospital, Taipei, 10449, Taiwan.
Abstract:
A number of the inhibitors against programmed death protein 1 (PD-1) have been approved to treat recurrent or metastatic squamous cell carcinoma of head and neck (HNSCC). The interaction between PD-1 and its ligand (PD-L1) serves as an immune checkpoint that governs cytotoxic immune effectors against tumors. Numerous clinical trials of PD-1/PD-L1 inhibitors have so far been discordant about having sufficient PD-L1 expression in the tumor as a prerequisite for a successful anti-PD-1 treatment. On the other hand, vascular endothelial cells modulate immune activities through PD-L1 expression, and thus it is possible that the expressions of circulating endothelial cells (CECs) and circulating endothelial progenitor cells (CPCs) could affect antitumor immunity as well as neoangiogenesis. Here we investigated the potential involvement of PD-L1+ CECs and PD-L1+ CPCs in PD-1 blockade treatments for HNSCC patients. We measured CD8+ T cells, CECs, and CPCs in the peripheral blood of the HNSCC patients treated by anti-PD-1 therapies. We found that their PD-L1+ CPC expression before anti-PD1 therapies was strongly correlated with treatment responses and overall survival. Moreover, if the first infusion of PD-1 inhibitors reduced ≥ 50% PD-L1+ CPCs, a significantly better outcome could be predicted. In these patients as well as in an animal model of oral cancer, Pd-l1+ CPC expression was associated with limited CD8+ T-cell infiltration into the tumors, and anti-PD-1 treatments also targeted Pd-l1+ CPCs and increased CD8+ T-cell infiltration. Our results highlight PD-L1+ CPC as a potential regulator in the anti-PD-1 treatments for HNSCC.
Insights
Circulating endothelial progenitor cells expressing PD-L1 (PD-L1+ CPCs) impact head and neck cancer treatment. High PD-L1+ CPC levels before therapy correlate with poor outcomes, but their reduction predicts better survival with PD-1 inhibitors.
Area of Science:
- Immunology
- Oncology
- Vascular Biology
Background:
- Programmed death protein 1 (PD-1) inhibitors are approved for head and neck squamous cell carcinoma (HNSCC).
- The role of PD-L1 expression on circulating cells, particularly endothelial cells and progenitor cells, in anti-PD-1 therapy response remains unclear.
- Vascular endothelial cells expressing PD-L1 can influence immune responses.
Purpose of the Study:
- To investigate the role of PD-L1-expressing circulating endothelial cells (CECs) and circulating endothelial progenitor cells (CPCs) in HNSCC patients undergoing PD-1 blockade therapy.
- To determine if PD-L1+ CECs and PD-L1+ CPCs correlate with treatment response and survival.
- To explore the impact of anti-PD-1 therapy on PD-L1+ CPCs and T-cell infiltration.
Main Methods:
- Measurement of CD8+ T cells, CECs, and CPCs in peripheral blood of HNSCC patients treated with anti-PD-1 therapies.
- Correlation analysis of PD-L1+ CPC expression with treatment response and overall survival.
- Assessment of PD-L1+ CPC levels and CD8+ T-cell infiltration in an oral cancer animal model.
Main Results:
- Pre-treatment PD-L1+ CPC expression strongly correlated with treatment response and overall survival in HNSCC patients.
- A reduction of ≥50% in PD-L1+ CPCs after the first anti-PD-1 infusion predicted significantly better outcomes.
- PD-L1+ CPC expression was associated with reduced CD8+ T-cell infiltration, which was increased by anti-PD-1 treatment targeting PD-L1+ CPCs.
Conclusions:
- PD-L1+ CPCs are potential regulators of anti-PD-1 therapy efficacy in HNSCC.
- PD-L1+ CPC levels can serve as a predictive biomarker for treatment response and survival.
- Targeting PD-L1+ CPCs may enhance anti-tumor immunity and improve outcomes in HNSCC patients treated with PD-1 inhibitors.
