Lung cancer’s molecular features shed light on immunotherapy response


Cancer cells (red), cell nuclei (cyan), stroma/desmoplasia (green), active stroma-specific marker (purple). Credit: National Cancer Institute 

One of the newest types of cancer drugs, immunotherapies called immune checkpoint inhibitors, has transformed the treatment of lung cancer over the last decade dramatically improving the survival of some patients with the most common form of this disease, non-small cell lung cancer (NSCLC). However, only about 20% of patients experience a benefit from these immunotherapies.  A study led by researchers at the Broad Institute of MIT and Harvard and Massachusetts General Hospital (MGH) reveals molecular features of lung tumors that could explain why some patients respond to these treatments while others do not. The team has pinpointed several genetic and other biological factors that may influence the response of NSCLC patients to immunotherapies that inhibit the PD-1 or PD-L1 proteins.

The research team examined whole-exome sequencing and RNA-sequencing data from tumor samples contributed by nearly 400 NSCLC patients before treatment, along with information about their clinical responses to anti-PD-(L)1 therapy. This is one of the largest multi-omic datasets from NSCLC patients who have been treated with these medicines, enabling the scientists to identify a suite of molecular features that are associated with improved treatment outcomes. Results demonstrate the complexity of the biological factors that determine immunotherapy response, and suggest why existing methods of predicting treatment outcomes in NSCLC patients, which look at only a small number of molecular features, aren’t always accurate. The researchers said their study points to the potential for improving these predictions or even developing more personalized approaches to treatment based on a patient’s molecular profile.

By Karen Zusi-Tran, Broad Institute of MIT and Harvard

Article can be accessed on: MedicalXpress