Spatial profiling of non-small cell lung cancer provides insights into tumorigenesis and immunotherapy response

This study investigates molecular changes in the response of NSCLC patients to ICI using spatial transcriptomics.

Activation of B cellassociated pathways correlates with improved prognosis and guides personalized immunotherapy approaches in NSCLC.

Lung cancer is the second most common cancer worldwide and a leading cause of cancer-related deaths.

Despite advances in targeted therapy and immunotherapy, the prognosis remains unfavorable, especially in metastatic cases.

This study aims to identify molecular changes in non-small cell lung cancer (NSCLC) patients based on their response to treatment.

Using tumor and matched immune cell rich peritumoral tissues, we perform a retrospective, comprehensive spatial transcriptomic analysis of a proven malignant NSCLC sample treated with immune checkpoint inhibitor (ICI).

In addition to T cells, other immune cell types, such as B cells and macrophages, were also activated in responders to ICI treatment.

In particular, B cells and B cell-mediated immunity pathways are consistently found to be activated.

Analysis of the histologic subgroup (lung squamous cell carcinoma, LUSC; lung adenocarcinoma, LUAD) of NSCLC also confirms activation of B cell mediated immunity.

Analysis of B cell subtypes shows that B cell subtypes were more activated in immune cell-rich tissues near tumor tissue.

Furthermore, increased expression of B cell immunity-related genes is associated with better prognosis.

These findings provide insight into predicting ICI treatment responses and identifying appropriate candidates for immunotherapy in NSCLC patients.