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Soluble PD-L1 and Circulating CD8+PD-1+ and NK Cells Enclose a Prognostic and Predictive Immune Effector Score in Immunotherapy Treated NSCLC patients.
- Source :
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Lung cancer (Amsterdam, Netherlands) [Lung Cancer] 2020 Oct; Vol. 148, pp. 1-11. Date of Electronic Publication: 2020 Aug 02. - Publication Year :
- 2020
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Abstract
- Introduction: Upfront criteria to foresee immune checkpoint inhibitors (ICIs) efficacy are far from being identified. Thus, we integrated blood descriptors of pro-inflammatory/immunosuppressive or effective anti-tumor response to non-invasively define predictive immune profiles in ICI-treated advanced non-small cell lung cancer (NSCLC).<br />Methods: Peripheral blood (PB) was prospectively collected at baseline from 109 consecutive NSCLC patients undergoing ICIs as first or more line treatment. Soluble PD-L1 (sPD-L1) (immunoassay), CD8+PD-1+ and NK (FACS) cells were assessed and interlaced to generate an Immune effector Score (I <subscript>eff</subscript> S). Lung Immune Prognostic Index (LIPI) was computed by LDH levels and derived Neutrophil-to-Lymphocyte Ratio (dNLR). All these parameters were correlated with survival outcome and treatment response.<br />Results: High sPD-L1 and low CD8+PD-1+ and NK number had negative impact on PFS (P < 0.001), OS (P < 0.01) and ICI-response (P < 0.05). Thus, sPD-L1 <superscript>high</superscript> , CD8+PD-1+ <superscript>low</superscript> and NK <superscript>low</superscript> were considered as risk factors encompassing I <subscript>eff</subscript> S, whose prognostic power outperformed that of individual features and slightly exceeded that of LIPI. Accordingly, the absence of these risk factors portrayed a favorable I <subscript>eff</subscript> S characterizing patients with significantly (P < 0.001) prolonged PFS (median NR vs 2.3 months) and OS (median NR vs 4.1) and greater benefit from ICIs (P < 0.01). We then combined each risk parameter composing I <subscript>eff</subscript> S and LIPI (LDH <superscript>high</superscript> , dNLR <superscript>high</superscript> ), thus defining three distinct prognostic classes. A remarkable impact of I <subscript>eff</subscript> S-LIPI integration was documented on survival outcome (PFS, HR = 4.61; 95%CI = 2.32-9.18; P < 0.001; OS, HR=4.03; 95%CI=1.91-8.67; P < 0.001) and ICI-response (AUC=0.90, 95%CI=0.81-0.97, P < 0.001).<br />Conclusion: Composite risk models based on blood parameters featuring the tumor-host interaction might provide accurate prognostic scores able to predict ICI benefit in NSCLC patients.<br /> (Copyright © 2020. Published by Elsevier B.V.)
Details
- Language :
- English
- ISSN :
- 1872-8332
- Volume :
- 148
- Database :
- MEDLINE
- Journal :
- Lung cancer (Amsterdam, Netherlands)
- Publication Type :
- Academic Journal
- Accession number :
- 32768804
- Full Text :
- https://doi.org/10.1016/j.lungcan.2020.07.028