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 path-ological 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 muta-tional burden seem to correlate better with higher pathological response rates and survival. Epidermal growth factor receptor, Serine/Threonine Kinase 11and 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, mi-crobiota, 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 re-sections in the early stage. 2023 Elsevier Ltd. All rights reserved.

Automated summary

Immunotherapy with immune-checkpoint inhibitors (ICIs) has revolutionised the treatment of advanced non-small cell lung cancer (NSCLC). It has shown promising results in early NSCLC, especially with neoadjuvant multimodality approaches. However, biomarkers for predicting response to ICIs in early-stage NSCLC are lacking. PD-L1 expression and tumor mutational burden seem to correlate with better response rates and survival. Other promising approaches include blood-based ratios, microbiota, and baseline intratumoral TCR clonality. Circulating tumor DNA could help in selecting best candidates for adjuvant ICIs and monitoring tumor response.