A signature of enhanced proliferation associated with response and survival to anti-PD-L1 therapy in early-stage non-small cell lung cancer

In early -stage non -small cell lung cancer, the combination of neoadjuvant anti -PD -L1 and subablative stereotactic body radiation therapy (SBRT) is associated with higher rates of major pathologic response compared to anti -PD -L1 alone. Here, we identify a 140 -gene set, enriched in genes characteristic of highly proliferating cells, associated with response to the dual therapy. Analysis of on -treatment transcriptome data indicate roles for T and B cells in response. The 140 -gene set is associated with disease -free survival when applied to the combined trial arms. This 140 -gene set identifies a subclass of tumors in all 7 of The Cancer Genome Atlas tumor types examined. Worse survival is associated with the 140 -gene signature in 5 of these tumor types. Collectively, our data support that this 140 -gene set, discovered in association with response to combined anti -PD -L1 and SBRT, identifies a clinically aggressive subclass of solid tumors that may be more likely to respond to immunotherapies.