Plasmacytoid Dendritic Cell, Slan+-Monocyte and Natural Killer Cell Counts Function as Blood Cell-Based Biomarkers for Predicting Responses to Immune Checkpoint Inhibitor Monotherapy in Non-Small Cell Lung Cancer Patients

浆细胞样树突状细胞、Slan+-单核细胞和自然杀伤细胞计数可作为血细胞生物标志物,用于预测非小细胞肺癌患者对免疫检查点抑制剂单药治疗的反应

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作者:Francesca Pettinella, Chiara Lattanzi, Marta Donini, Elena Caveggion, Olivia Marini, Giulia Iannoto, Sara Costa, Elena Zenaro, Tiago Moderno Fortunato, Sara Gasperini, Matteo Giani, Lorenzo Belluomini, Marco Sposito, Jessica Insolda, Ilaria Mariangela Scaglione, Michele Milella, Annalisa Adamo, Orne

Abstract

The advent of immune checkpoint inhibitors (ICIs), for instance, programmed cell death 1 (PD-1)/PD-1 ligand 1 (PD-L1) blockers, has greatly improved the outcome of patients affected by non-small cell lung cancer (NSCLC). However, most NSCLC patients either do not respond to ICI monotherapy or develop resistance to it after an initial response. Therefore, the identification of biomarkers for predicting the response of patients to ICI monotherapy represents an urgent issue. Great efforts are currently dedicated toward identifying blood-based biomarkers to predict responses to ICI monotherapy. In this study, more commonly utilized blood-based biomarkers, such as the neutrophil-to-lymphocyte ratio (NLR) and the lung immune prognostic index (LIPI) score, as well as the frequency/number and activation status of various types of circulating innate immune cell populations, were evaluated in NSCLC patients at baseline before therapy initiation. The data indicated that, among all the parameters tested, low plasmacytoid dendritic cell (pDC), slan+-monocyte and natural killer cell counts, as well as a high LIPI score and elevated PD-L1 expression levels on type 1 conventional DCs (cDC1s), were independently correlated with a negative response to ICI therapy in NSCLC patients. The results from this study suggest that the evaluation of innate immune cell numbers and phenotypes may provide novel and promising predictive biomarkers for ICI monotherapy in NSCLC patients.

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