Altorki et al. interrogated RNAseq data from 16 pre-treatment NSCLC tumors and identified a molecular subclass of early-stage NSCLC based on 140 differentially expressed genes associated with a high proliferative index (PI) and a good response to neoadjuvant combination anti-PD-L1 and sub-ablative stereotactic body radiation therapy. High PI tumors showed features of immunosuppressive TMEs, including increased cancer cell PD-L1 expression, reduced MHC class II expression, and increased abundance of Tregs. In 6 of 7 tumors analyzed in TCGA, the 140-gene set identified a high PI subclass, and was associated with worse survival.
Contributed by Shishir Pant
ABSTRACT: 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.
Author Info: (1) Meyer Cancer Center, Weill Cornell Medicine and New York Presbyterian Hospital, New York, NY 10065, USA; Department of Cardiothoracic Surgery, Weill Cornell Medicine and New Yo
Author Info: (1) Meyer Cancer Center, Weill Cornell Medicine and New York Presbyterian Hospital, New York, NY 10065, USA; Department of Cardiothoracic Surgery, Weill Cornell Medicine and New York Presbyterian Hospital, New York, NY 10065, USA. Electronic address: nkaltork@med.cornell.edu. (2) Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY 10065, USA; Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, USA. (3) Department of Pathology and Laboratory Medicine, Northwell Health Cancer Institute, Northwell Health, Greenvale, NY 10042, USA. (4) Meyer Cancer Center, Weill Cornell Medicine and New York Presbyterian Hospital, New York, NY 10065, USA; Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY 10065, USA; Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, USA. (5) Meyer Cancer Center, Weill Cornell Medicine and New York Presbyterian Hospital, New York, NY 10065, USA; Department of Cardiothoracic Surgery, Weill Cornell Medicine and New York Presbyterian Hospital, New York, NY 10065, USA. (6) Meyer Cancer Center, Weill Cornell Medicine and New York Presbyterian Hospital, New York, NY 10065, USA; Department of Cardiothoracic Surgery, Weill Cornell Medicine and New York Presbyterian Hospital, New York, NY 10065, USA; Department of Biochemistry, Weill Cornell Medicine, New York, NY 10065, USA. Electronic address: temcgraw@med.cornell.edu.
