Association of High Tumor Mutation Burden in Non–Small Cell Lung Cancers With Increased Immune Infiltration and Improved Clinical Outcomes of PD-L1 Blockade Across PD-L1 Expression Levels
Biagio Ricciuti,Xinan Wang,Joao Victor Machado Alessi,Hira Rizvi,Navin R. Mahadevan,Yvonne Y. Li,Andrew Polio,James Lindsay,Renato Umeton,Rileen Sinha,Natalie I. Vokes,Gonzalo Recondo,Giuseppe Lamberti,Marissa N. Lawrence,V. Vaz,Giulia Costanza Leonardi,Andrew J. Plodkowski,Hersh Gupta,Andrew D. Cherniack,Michael Y. Tolstorukov,Bijaya Sharma,Kristen Felt,Justin F. Gainor,Arvind Ravi,Gad Getz,Kurt A. Schalper,Brian Henick,Patrick M. Forde,Valsamo Anagnostou,Pasi A. Jänne,Eliezer M. Van Allen,Mizuki Nishino,Lynette M. Sholl,David C. Christiani,Xihong Lin,Scott J. Rodig,Matthew D. Hellmann,Mark M. Awad +37 more
TLDR
It is suggested that in NSCLC, a high number of nonsynonymous tumor mutations is associated with immune cell infiltration and inflammatory T-cell expression signatures, leading to increased sensitivity to PD-1/PD-L1 inhibition across PD-L 1 expression subgroups.Abstract:
Key Points Question Is tumor mutation burden (TMB) associated with improved outcomes of programmed cell death–1 (PD-1)/programmed death ligand–1 (PD-L1) inhibition across PD-L1 expression levels in non–small cell lung cancer (NSCLC)? Findings In this cohort study of 1552 patients with NSCLC, the group with high TMB had improved response rates and survival after receiving PD-1/PD-L1 inhibition therapy across PD-L1 expression subgroups compared with the group with low TMB. High TMB levels were associated with increased CD8-positive T-cell infiltration and distinct immune response gene expression signatures. Meaning These findings suggest that in NSCLC, a high number of nonsynonymous tumor mutations is associated with immune cell infiltration and inflammatory T-cell expression signatures, leading to increased sensitivity to PD-1/PD-L1 inhibition across PD-L1 expression subgroups.read more
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