Biomarkers of response to immunotherapy in early stage non-small cell lung cancer.

Immunotherapy with immune-checkpoint inhibitors (ICIs) targeting programmed cell death 1 or programmed death-ligand 1 has revolutionised the treatment of advanced non-small cell lung cancer (NSCLC) and has been investigated in early NSCLC, alone or in combination with chemotherapy, anti-CTLA-4 antibodies and radiotherapy. Although more mature data are needed before setting a change of paradigm in early stages, reports of pathological response rates and disease-free survival are promising, especially with neoadjuvant multimodality approaches. Nevertheless, major pathological response rates for neoadjuvant anti-PD-(L)1 monotherapy rarely exceed 40%, and biomarkers for characterising patients who may benefit the most from ICIs are lacking. These biomarkers have a distinct value from the metastatic setting, with highly different tumour biologies. Among the most investigated so far in this context, programmed death-ligand 1 expression and, to a lesser extent, tumour mutational burden seem to correlate better with higher pathological response rates and survival. Epidermal growth factor receptor , Serine/Threonine Kinase 11 and Kelch-like ECH-associated protein 1 mutations rise as essential determinations for the treatment selection in early-stage NSCLC. Emerging and promising approaches comprise evaluation of blood-based ratios, microbiota, and baseline intratumoural TCR clonality. Circulating tumour DNA will be of great help in the near future when selecting best candidates for adjuvant ICIs, monitoring the tumour response to the neoadjuvant treatment in order to improve the rates of complete resections in the early stage. • Immune-checkpoint inhibitors (ICIs)are becoming a standard in early non-small cell lung cancer but do not benefit all patients. • Programmed death-ligand 1 expression and tumour mutational burden are the better-documented biomarkers. • Patients with epidermal growth factor receptor , Serine/Threonine Kinase 11 or Kelch-like ECH-associated protein 1 alterations yield poor benefit from ICIs. • Emerging biomarkers include TCR clonality, microbiota and blood-based ratios. • Circulating tumour DNA is a reliable tool to evaluate disease burden following surgery or ICIs. [ABSTRACT FROM AUTHOR]