Biomarkers of success of anti-PD-(L)1 immunotherapy for non-small cell lung cancer derived from RNA- and whole-exome sequencing: results of a prospective observational study on a cohort of 85 patients

作者：Elena Poddubskaya, Maria Suntsova, Marina A. Lyadova, Daniil Luppov, Anastasia Guryanova, Vladimir Lyadov, Andrew Garazha, Maxim Sorokin, Anna Semenova, V.G. Shatalov, M. Biakhova, Alexander Simonov, Aleksey Moisseev, Anton Buzdin · 发表于：Frontiers in Immunology · 年份：2024 · DOI：10.3389/fimmu.2024.1493877 · 被引用次数：7 · 研究领域：Cancer Immunotherapy and Biomarkers、Ferroptosis and cancer prognosis、Cancer, Stress, Anesthesia, and Immune Response

Background: Immune checkpoint inhibitors (ICIs) treatment have shown high efficacy for about 15 cancer types. However, this therapy is only effective in 20-30% of cancer patients. Thus, the precise biomarkers of ICI response are an urgent need. Methods: We conducted a prospective observational study of the prognostic potential ofseveral existing and putative biomarkers of response to immunotherapy in acohort of 85 patients with lung cancer (LC) receiving PD-1 or PD-L1 targeted ICIs. Tumor biosamples were obtained prior to ICI treatment and profiled by whole exome and RNA sequencing. The entire 403 putative biomarkers were screened, including tumor mutation burden (TMB) and number of cancer neoantigens, 131 specific HLA alleles, homozygous state of 11 HLA alleles and their superfamilies; four gene mutation biomarkers, expression of 45 immune checkpoint genes and closely related genes, and three previously published diagnostic gene signatures; for the first time, activation levels of 188 molecular pathways containing immune checkpoint genes and activation levels of 19 pathways algorithmically generated using a human interactome model centered around immune checkpoint genes. Treatment outcomes and/or progression-free survival (PFS) times were available for 61 of 85 patients with LC, including 24 patients with adenocarcinoma and 27 patients with squamous cell LC, whose samples were further analyzed. For the rest 24 patients, both treatment outcomes and PFS data could not be colle...