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Using 22C3 Anti-PD-L1 Antibody Concentrate on Biopsy and Cytology Samples from Non-small Cell Lung Cancer Patients
Published on: September 25, 2018
Heterogeneity of PD-L1 Expression Between the Primary Tumor and Matched Lymph Node Metastases in Head and Neck
Moritz Knebel1,2, Gilbert Georg Klamminger3,4, Jan Philipp Kühn1,2
1Institute of Otorhinolaryngology, Saarland University, 66421 Homburg, Germany.
Abstract:
Background: The role of immune checkpoint inhibition in treating head and neck squamous cell carcinoma (HNSCC) is expanding, yet response rates to PD-L1 therapy remain inconsistent and generally poor. Although several studies have examined heterogeneous intratumoral PD-L1 expression, the disparity in response to PD-L1 therapy between primary tumors and their associated lymph node metastases remains unclear. Methods: Primary tumor samples and two matching lymph node metastases were obtained from a cohort of 50 patients and immunohistochemically stained with a PD-L1 antibody. PD-L1 expression, assessed using the combined positive score (CPS) and tumor proportion score (TPS), and immune infiltration, measured with an immunoreactive score (IRS), were compared between the primary tumor and lymph node metastases. These measures were then correlated with other histopathological and clinical features. Results: PD-L1 expression, evaluated by CPS and TPS, showed no significant differences between the primary tumor and matched lymph node metastases. Discordance relative to established regulatory cut-offs was observed in a subset of patients, affecting 18% (CPS; 95% CI, 8.0-30.0%) and 4% (TPS; 95% CI, 0.0-10.0%) of cases. CPS and TPS values were not influenced by primary tumor subsite or HPV status. Conversely, immune infiltration measured by IRS was significantly affected by primary tumor subsite location. Both HPV tumor status and primary tumor subsite were statistically significantly associated with overall survival. Conclusions: Our findings highlight variability in PD-L1 expression in HNSCC and may offer context for differential responses of primary tumors and lymph node metastases to immune checkpoint therapy reported in recent clinical studies. These observations support the need for a more comprehensive characterization of PD-L1 expression across tumor sites in head and neck cancer. Further investigation is required to determine whether, and in which settings, reassessment of PD-L1 status in metastatic lesions-including lymph node metastases-may provide additional clinically relevant information when initial testing does not meet established therapeutic cut-offs.
Insights
PD-L1 expression in head and neck squamous cell carcinoma (HNSCC) primary tumors and lymph node metastases showed no significant differences. However, variability exists, impacting treatment decisions for immune checkpoint therapy.
Area of Science:
- Oncology
- Immunology
- Pathology
Background:
- Immune checkpoint inhibitors targeting PD-L1 are increasingly used for head and neck squamous cell carcinoma (HNSCC).
- Response rates to PD-L1 therapy in HNSCC are inconsistent, and the role of PD-L1 expression in primary tumors versus lymph node metastases is unclear.
Purpose of the Study:
- To compare PD-L1 expression (CPS and TPS) and immune infiltration (IRS) between primary HNSCC tumors and matched lymph node metastases.
- To correlate these measures with histopathological and clinical features, including HPV status and tumor subsite.
Main Methods:
- Immunohistochemical staining for PD-L1 on primary tumors and lymph node metastases from 50 HNSCC patients.
- Assessment of PD-L1 expression using Combined Positive Score (CPS) and Tumor Proportion Score (TPS).
- Measurement of immune infiltration using Immunoreactive Score (IRS) and correlation with clinical data.
Main Results:
- No significant differences in PD-L1 expression (CPS, TPS) were found between primary tumors and lymph node metastases.
- Discordance in PD-L1 expression relative to therapeutic cut-offs was observed in 18% (CPS) and 4% (TPS) of cases.
- Immune infiltration (IRS) varied significantly by primary tumor subsite, and HPV status and tumor subsite were associated with overall survival.
Conclusions:
- PD-L1 expression is variable in HNSCC, potentially explaining differential responses to immune checkpoint therapy between primary sites and metastases.
- Comprehensive characterization of PD-L1 expression across tumor sites is needed for HNSCC.
- Further research should explore the clinical utility of reassessing PD-L1 status in metastatic lesions when initial testing is below therapeutic thresholds.
