In Nature Genetics, investigators at the Broad institute, Dana-Farber Cancer Institute, and elsewhere consider features of non-small lung cancer (NSCLC) linked to checkpoint immunotherapy response. As part of a Stand Up to Cancer-Mark Foundation analysis, the team analyzed tumor exome and/or RNA sequence data in combination with clinical outcome profiles for 393 advanced NSCLC patients receiving anti-PD-1/PD-L1 checkpoint inhibitor treatment, highlighting several molecular features linked to better or worse progression-free survival and overall survival outcomes. Among other response-related features, their results suggest that TERT amplifications tend to coincide with poorer outcomes, for example, while alterations affecting the ATM gene; increased expression of immunoproteasome-related genes such as PSME1, PSME2, and PSMB9; or expression features resembling a dedifferentiated tumor subtype were linked to more favorable outcomes. "Comprehensive identification of predictors of checkpoint blockade response in patients with NSCLC has been limited by the availability of large, well-annotated patient cohorts with matched genomic data, particularly within individual cancer types," the authors explain, noting that findings from the current analysis suggest a "complex interplay between distinct signaling pathways (for example, CXCL9 versus TGF-beta signaling) and distinct cell types (for example, myeloid cells versus fibroblasts), shedding light on some of the multifaceted interactions underlying checkpoint blockade responsiveness."
Lung Cancer Study Finds Molecular Features Affecting Immunotherapy Response
Apr 10, 2023