Soluble PD-L1 and Circulating CD8+PD-1+ and NK Cells Enclose a Prognostic and Predictive Immune Effector Score in Immunotherapy Treated NSCLC patients
•Immune checkpoint inhibitors (ICIs) have shifted the therapeutic approach to NSCLC•Reproducible biomarkers of ICI benefit represent an unmet and urgent need•Circulating descriptors of cancer-host immune interaction were explored here•sPD-L1, CD8+PD-1+ and NK cells enclosed a highly prognostic immun...
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| Veröffentlicht in: | Lung cancer (Amsterdam, Netherlands) Netherlands), 2020-10, Vol.148, p.1-11 |
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| creator | Mazzaschi, G. Minari, R. Zecca, A. Cavazzoni, A. Ferri, V. Mori, C. Squadrilli, A. Bordi, P. Buti, S. Bersanelli, M. Leonetti, A. Cosenza, A Ferri, L. Rapacchi, E. Missale, G. Petronini, P.G. Quaini, F. Tiseo, M |
| description | •Immune checkpoint inhibitors (ICIs) have shifted the therapeutic approach to NSCLC•Reproducible biomarkers of ICI benefit represent an unmet and urgent need•Circulating descriptors of cancer-host immune interaction were explored here•sPD-L1, CD8+PD-1+ and NK cells enclosed a highly prognostic immune effector score•Blood-based multiparametric models might non-invasively predict ICI response
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).
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 (IeffS). 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.
High sPD-L1 and low CD8+PD-1+ and NK number had negative impact on PFS (P |
| doi_str_mv | 10.1016/j.lungcan.2020.07.028 |
| format | Article |
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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).
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 (IeffS). 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.
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-L1high, CD8+PD-1+low and NKlow were considered as risk factors encompassing IeffS, whose prognostic power outperformed that of individual features and slightly exceeded that of LIPI. Accordingly, the absence of these risk factors portrayed a favorable IeffS 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 IeffS and LIPI (LDHhigh, dNLRhigh), thus defining three distinct prognostic classes. A remarkable impact of IeffS-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).
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.]]></description><identifier>ISSN: 0169-5002</identifier><identifier>EISSN: 1872-8332</identifier><identifier>DOI: 10.1016/j.lungcan.2020.07.028</identifier><identifier>PMID: 32768804</identifier><language>eng</language><publisher>Ireland: Elsevier B.V</publisher><subject>B7-H1 Antigen ; Carcinoma, Non-Small-Cell Lung - therapy ; CD8-Positive T-Lymphocytes ; circulating biomarkers ; Humans ; immune checkpoint inhibitors ; Immunotherapy ; Killer Cells, Natural ; Lung Neoplasms - therapy ; non-small cell lung cancer ; Prognosis ; prognostic scores ; Programmed Cell Death 1 Receptor</subject><ispartof>Lung cancer (Amsterdam, Netherlands), 2020-10, Vol.148, p.1-11</ispartof><rights>2020</rights><rights>Copyright © 2020. Published by Elsevier B.V.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c431t-5cd6093022d78edacaccdca262d2adeff7f950ba9f42560d55c90b962f845d723</citedby><cites>FETCH-LOGICAL-c431t-5cd6093022d78edacaccdca262d2adeff7f950ba9f42560d55c90b962f845d723</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.lungcan.2020.07.028$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32768804$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mazzaschi, G.</creatorcontrib><creatorcontrib>Minari, R.</creatorcontrib><creatorcontrib>Zecca, A.</creatorcontrib><creatorcontrib>Cavazzoni, A.</creatorcontrib><creatorcontrib>Ferri, V.</creatorcontrib><creatorcontrib>Mori, C.</creatorcontrib><creatorcontrib>Squadrilli, A.</creatorcontrib><creatorcontrib>Bordi, P.</creatorcontrib><creatorcontrib>Buti, S.</creatorcontrib><creatorcontrib>Bersanelli, M.</creatorcontrib><creatorcontrib>Leonetti, A.</creatorcontrib><creatorcontrib>Cosenza, A</creatorcontrib><creatorcontrib>Ferri, L.</creatorcontrib><creatorcontrib>Rapacchi, E.</creatorcontrib><creatorcontrib>Missale, G.</creatorcontrib><creatorcontrib>Petronini, P.G.</creatorcontrib><creatorcontrib>Quaini, F.</creatorcontrib><creatorcontrib>Tiseo, M</creatorcontrib><title>Soluble PD-L1 and Circulating CD8+PD-1+ and NK Cells Enclose a Prognostic and Predictive Immune Effector Score in Immunotherapy Treated NSCLC patients</title><title>Lung cancer (Amsterdam, Netherlands)</title><addtitle>Lung Cancer</addtitle><description><![CDATA[•Immune checkpoint inhibitors (ICIs) have shifted the therapeutic approach to NSCLC•Reproducible biomarkers of ICI benefit represent an unmet and urgent need•Circulating descriptors of cancer-host immune interaction were explored here•sPD-L1, CD8+PD-1+ and NK cells enclosed a highly prognostic immune effector score•Blood-based multiparametric models might non-invasively predict ICI response
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).
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 (IeffS). 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.
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-L1high, CD8+PD-1+low and NKlow were considered as risk factors encompassing IeffS, whose prognostic power outperformed that of individual features and slightly exceeded that of LIPI. Accordingly, the absence of these risk factors portrayed a favorable IeffS 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 IeffS and LIPI (LDHhigh, dNLRhigh), thus defining three distinct prognostic classes. A remarkable impact of IeffS-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).
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.]]></description><subject>B7-H1 Antigen</subject><subject>Carcinoma, Non-Small-Cell Lung - therapy</subject><subject>CD8-Positive T-Lymphocytes</subject><subject>circulating biomarkers</subject><subject>Humans</subject><subject>immune checkpoint inhibitors</subject><subject>Immunotherapy</subject><subject>Killer Cells, Natural</subject><subject>Lung Neoplasms - therapy</subject><subject>non-small cell lung cancer</subject><subject>Prognosis</subject><subject>prognostic scores</subject><subject>Programmed Cell Death 1 Receptor</subject><issn>0169-5002</issn><issn>1872-8332</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU9vEzEQxS0EoqHwEUA-IlW7jL3_TwhtQ1sRQaSUs-XYs8HRrh1sb6V-ET5vnSZw5TSH95t5mvcIec8gZ8DqT_t8nO1OSZtz4JBDkwNvX5AFaxuetUXBX5JF4rqsAuAX5E0IewDWMOhek4uCN3XbQrkgfzZunLcj0vV1tmJUWk1749U8ymjsjvbX7VVS2NWz8v0b7XEcA11aNbqAVNK1dzvrQjTqmVh71EZF84D0bppmi3Q5DKii83SjnEdq7Elw8Rd6eXik9x5lxHR70696eki2aGN4S14Ncgz47jwvyc-vy_v-Nlv9uLnrv6wyVRYsZpXSNXQFcK6bFrVUUimtJK-55lLjMDRDV8FWdkPJqxp0VakOtl3Nh7asdMOLS_LxdPfg3e8ZQxSTCSr9KC26OQiebFpeN-URrU6o8i4Ej4M4eDNJ_ygYiGMlYi_OlYhjJQIakSpJex_OFvN2Qv1v628HCfh8AjA9-mDQi6BSCCol6VN0QjvzH4sn4imflA</recordid><startdate>202010</startdate><enddate>202010</enddate><creator>Mazzaschi, G.</creator><creator>Minari, R.</creator><creator>Zecca, A.</creator><creator>Cavazzoni, A.</creator><creator>Ferri, V.</creator><creator>Mori, C.</creator><creator>Squadrilli, A.</creator><creator>Bordi, P.</creator><creator>Buti, S.</creator><creator>Bersanelli, M.</creator><creator>Leonetti, A.</creator><creator>Cosenza, A</creator><creator>Ferri, L.</creator><creator>Rapacchi, E.</creator><creator>Missale, G.</creator><creator>Petronini, P.G.</creator><creator>Quaini, F.</creator><creator>Tiseo, M</creator><general>Elsevier B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>202010</creationdate><title>Soluble PD-L1 and Circulating CD8+PD-1+ and NK Cells Enclose a Prognostic and Predictive Immune Effector Score in Immunotherapy Treated NSCLC patients</title><author>Mazzaschi, G. ; Minari, R. ; Zecca, A. ; Cavazzoni, A. ; Ferri, V. ; Mori, C. ; Squadrilli, A. ; Bordi, P. ; Buti, S. ; Bersanelli, M. ; Leonetti, A. ; Cosenza, A ; Ferri, L. ; Rapacchi, E. ; Missale, G. ; Petronini, P.G. ; Quaini, F. ; Tiseo, M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c431t-5cd6093022d78edacaccdca262d2adeff7f950ba9f42560d55c90b962f845d723</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>B7-H1 Antigen</topic><topic>Carcinoma, Non-Small-Cell Lung - therapy</topic><topic>CD8-Positive T-Lymphocytes</topic><topic>circulating biomarkers</topic><topic>Humans</topic><topic>immune checkpoint inhibitors</topic><topic>Immunotherapy</topic><topic>Killer Cells, Natural</topic><topic>Lung Neoplasms - therapy</topic><topic>non-small cell lung cancer</topic><topic>Prognosis</topic><topic>prognostic scores</topic><topic>Programmed Cell Death 1 Receptor</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mazzaschi, G.</creatorcontrib><creatorcontrib>Minari, R.</creatorcontrib><creatorcontrib>Zecca, A.</creatorcontrib><creatorcontrib>Cavazzoni, A.</creatorcontrib><creatorcontrib>Ferri, V.</creatorcontrib><creatorcontrib>Mori, C.</creatorcontrib><creatorcontrib>Squadrilli, A.</creatorcontrib><creatorcontrib>Bordi, P.</creatorcontrib><creatorcontrib>Buti, S.</creatorcontrib><creatorcontrib>Bersanelli, M.</creatorcontrib><creatorcontrib>Leonetti, A.</creatorcontrib><creatorcontrib>Cosenza, A</creatorcontrib><creatorcontrib>Ferri, L.</creatorcontrib><creatorcontrib>Rapacchi, E.</creatorcontrib><creatorcontrib>Missale, G.</creatorcontrib><creatorcontrib>Petronini, P.G.</creatorcontrib><creatorcontrib>Quaini, F.</creatorcontrib><creatorcontrib>Tiseo, M</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Lung cancer (Amsterdam, Netherlands)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mazzaschi, G.</au><au>Minari, R.</au><au>Zecca, A.</au><au>Cavazzoni, A.</au><au>Ferri, V.</au><au>Mori, C.</au><au>Squadrilli, A.</au><au>Bordi, P.</au><au>Buti, S.</au><au>Bersanelli, M.</au><au>Leonetti, A.</au><au>Cosenza, A</au><au>Ferri, L.</au><au>Rapacchi, E.</au><au>Missale, G.</au><au>Petronini, P.G.</au><au>Quaini, F.</au><au>Tiseo, M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Soluble PD-L1 and Circulating CD8+PD-1+ and NK Cells Enclose a Prognostic and Predictive Immune Effector Score in Immunotherapy Treated NSCLC patients</atitle><jtitle>Lung cancer (Amsterdam, Netherlands)</jtitle><addtitle>Lung Cancer</addtitle><date>2020-10</date><risdate>2020</risdate><volume>148</volume><spage>1</spage><epage>11</epage><pages>1-11</pages><issn>0169-5002</issn><eissn>1872-8332</eissn><abstract><![CDATA[•Immune checkpoint inhibitors (ICIs) have shifted the therapeutic approach to NSCLC•Reproducible biomarkers of ICI benefit represent an unmet and urgent need•Circulating descriptors of cancer-host immune interaction were explored here•sPD-L1, CD8+PD-1+ and NK cells enclosed a highly prognostic immune effector score•Blood-based multiparametric models might non-invasively predict ICI response
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).
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 (IeffS). 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.
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-L1high, CD8+PD-1+low and NKlow were considered as risk factors encompassing IeffS, whose prognostic power outperformed that of individual features and slightly exceeded that of LIPI. Accordingly, the absence of these risk factors portrayed a favorable IeffS 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 IeffS and LIPI (LDHhigh, dNLRhigh), thus defining three distinct prognostic classes. A remarkable impact of IeffS-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).
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.]]></abstract><cop>Ireland</cop><pub>Elsevier B.V</pub><pmid>32768804</pmid><doi>10.1016/j.lungcan.2020.07.028</doi><tpages>11</tpages></addata></record> |
| fulltext | fulltext |
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| ispartof | Lung cancer (Amsterdam, Netherlands), 2020-10, Vol.148, p.1-11 |
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| subjects | B7-H1 Antigen Carcinoma, Non-Small-Cell Lung - therapy CD8-Positive T-Lymphocytes circulating biomarkers Humans immune checkpoint inhibitors Immunotherapy Killer Cells, Natural Lung Neoplasms - therapy non-small cell lung cancer Prognosis prognostic scores Programmed Cell Death 1 Receptor |
| title | Soluble PD-L1 and Circulating CD8+PD-1+ and NK Cells Enclose a Prognostic and Predictive Immune Effector Score in Immunotherapy Treated NSCLC patients |
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