Soluble biomarkers to predict clinical outcomes in non-small cell lung cancer treated by immune checkpoints inhibitors

Abstract

Lung cancer remains the first cause of cancer-related death despite many therapeutic innovations, including immune checkpoint inhibitors (ICI). ICI are now well used in daily practice at late metastatic stages and locally advanced stages after a chemo-radiation. ICI are also emerging in the peri-operative context. However, all patients do not benefit from ICI and even suffer from additional immune side effects. A current challenge remains to identify patients eligible for ICI and benefiting from these drugs. Currently, the prediction of ICI response is only supported by Programmed death-ligand 1 (PD-L1) tumor expression with perfectible results and limitations inherent to tumor-biopsy specimen analysis. Here, we reviewed alternative markers based on liquid biopsy and focused on the most promising biomarkers to modify clinical practice, including non-tumoral blood cell count such as absolute neutrophil counts, platelet to lymphocyte ratio, neutrophil to lymphocyte ratio, and derived neutrophil to lymphocyte ratio. We also discussed soluble-derived immune checkpoint-related products such as sPD-L1, circulating tumor cells (detection, count, and marker expression), and circulating tumor DNA-related products. Finally, we explored perspectives for liquid biopsies in the immune landscape and discussed how they could be implemented into lung cancer management with a potential biological–driven decision.

Combining Classic and Novel Neutrophil-Related Biomarkers to Identify Non-Small-Cell Lung Cancer

“…Thus, our research underscores the importance of neutrophil-related biomarkers in predicting NSCLC risk, offering valuable assistance in clinical diagnosis. NLR, a parameter derived from the NEU divided by the LYM, is one of the most widely investigated features based on blood cell counts and serves as an indicator of systemic inflammation [36]. NLR captures the balance between the detrimental effects of increased neutrophils and the beneficial roles of adaptive immunity mediated by lymphocytes [37].…”

“…In the field of cancer research, NLR serves as an effective indicator of the dynamic balance between pro-tumor and anti-tumor responses in the body. Most published studies have mainly focused on the correlation between NLR and the prognosis of NSCLC [36][37][38][39][40], with little attention paid to its association with disease risk. Therese Haugdahl Nøst et al conducted a study on approximately 440,000 participants based on data from the UK Biobank, evaluating the longitudinal relationships between four systemic inflammation indicators (NLR, systemic immune-inflammation index, platelet-to-lymphocyte ratio, lymphocyte-tomonocyte ratio) and the risk of 17 cancer sites diagnosed clinically in the years preceding the study [41].…”

Soluble Programmed Death-Ligand 1 (sPD-L1) as a Promising Marker for Head and Neck Squamous Cell Carcinoma: Correlations With Clinical and Demographic Characteristics

“…Several research studies have explored the correlation between sPD-L1 levels and clinical factors in individuals with HNSCC. Research by Ancel et al has shown that high sPD-L1 levels in patients with non-small-cell lung cancer are associated with advanced stages of the disease and worse survival rates [ 43 ]. Similarly, Xu et al found that patients with advanced solid tumors tend to have higher levels of PD-L1 [ 44 ].…”

A Potential Biomarker of Dynamic Change in Peripheral CD45RA−CD27+CD127+ Central Memory T Cells for Anti-PD-1 Therapy in Patients with Esophageal Squamous Cell Carcinoma

“…NLR has been used as an indicator of chronic inflammation and general immune response, and may contribute to evaluation of tumor response in patients treated with immunotherapy [22]. Therefore, we also evaluated the NLR among cStages, treatment strategies, and pathological response of neoadjuvant therapy.…”