TMIC-28. TITLE: AN IMMUNE-RELATED, SEX-SPECIFIC T-CELL SIGNATURE IN GLIOBLASTOMA MICROENVIRONMENT WITH PROGNOSTIC IMPACT

TMIC-28. TITLE: AN IMMUNE-RELATED, SEX-SPECIFIC T-CELL SIGNATURE IN GLIOBLASTOMA MICROENVIRONMENT WITH PROGNOSTIC IMPACT

Abstract BACKGROUND Glioblastoma, IDH-wildtype (GBM), is the most prevalent and aggressive primary brain cancer with a poor prognosis. Immune checkpoint inhibitors (ICIs) have been explored in GBM with limited success, highlighting the need for a better understanding of the tumor microenvironment (T...

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Veröffentlicht in:Neuro-oncology (Charlottesville, Va.) Va.), 2024-11, Vol.26 (Supplement_8), p.viii303-viii304
Hauptverfasser: Romagnoli, Giulia, Offi, Martina, Capone, Imerio, Tavilla, Andrea, Canini, Irene, Lapenta, Caterina, Buccarelli, Mariachiara, Giordano, Martina, Tirelli, Valentina, Sanchez, Massimo, Fragale, Alessandra, Giannetti, Stefano, Ceccarelli, Giovanni Maria, Bonaventura, Rina Di, Doglietto, Francesco, Olivi, Alessandro, Lauretti, Liverana, Biffoni, Mauro, Ricci-Vitiani, Lucia, Pallini, Roberto, Gabriele, Lucia, D’Alessandris, Quintino Giorgio
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container_issue Supplement_8
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container_title Neuro-oncology (Charlottesville, Va.)
container_volume 26
creator Romagnoli, Giulia
Offi, Martina
Capone, Imerio
Tavilla, Andrea
Canini, Irene
Lapenta, Caterina
Buccarelli, Mariachiara
Giordano, Martina
Tirelli, Valentina
Sanchez, Massimo
Fragale, Alessandra
Giannetti, Stefano
Ceccarelli, Giovanni Maria
Bonaventura, Rina Di
Doglietto, Francesco
Olivi, Alessandro
Lauretti, Liverana
Biffoni, Mauro
Ricci-Vitiani, Lucia
Pallini, Roberto
Gabriele, Lucia
D’Alessandris, Quintino Giorgio
description Abstract BACKGROUND Glioblastoma, IDH-wildtype (GBM), is the most prevalent and aggressive primary brain cancer with a poor prognosis. Immune checkpoint inhibitors (ICIs) have been explored in GBM with limited success, highlighting the need for a better understanding of the tumor microenvironment (TME). This study investigated whether the expression of specific immune checkpoints on tissue-resident memory T cells (Trm) predicts patient outcomes. METHODS In a single cohort observational study, tumor samples from 45 histologically confirmed GBM patients were processed to obtain single-cell suspensions. Multiparametric flow cytometry was used to analyze the correlation of Trm phenotypes with overall survival (OS) and progression-free survival (PFS). Univariate and multivariate analyses were conducted to assess the prognostic significance of Trm subsets. RESULTS Low frequency of exausted Trm expressing programmed cell death protein 1 (PD1) and T cell immunoglobulin and mucin domain-containing protein 3 (TIM3) was associated with better clinical outcomes. Multivariate analysis identified low CD8+CD103+PD1+TIM3+ Trm and Karnofsky performance status (KPS) ≥70 as the most significant independent prognostic factors for longer OS (hazard ratios—HR [95%CI]: 0.14 [0.04–0.52] p < 0.001, 0.39 [0.16–0.96] p = 0.04, respectively). Additionally, younger patients (
doi_str_mv 10.1093/neuonc/noae165.1206
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TITLE: AN IMMUNE-RELATED, SEX-SPECIFIC T-CELL SIGNATURE IN GLIOBLASTOMA MICROENVIRONMENT WITH PROGNOSTIC IMPACT</title><source>Oxford University Press Journals All Titles (1996-Current)</source><creator>Romagnoli, Giulia ; Offi, Martina ; Capone, Imerio ; Tavilla, Andrea ; Canini, Irene ; Lapenta, Caterina ; Buccarelli, Mariachiara ; Giordano, Martina ; Tirelli, Valentina ; Sanchez, Massimo ; Fragale, Alessandra ; Giannetti, Stefano ; Ceccarelli, Giovanni Maria ; Bonaventura, Rina Di ; Doglietto, Francesco ; Olivi, Alessandro ; Lauretti, Liverana ; Biffoni, Mauro ; Ricci-Vitiani, Lucia ; Pallini, Roberto ; Gabriele, Lucia ; D’Alessandris, Quintino Giorgio</creator><creatorcontrib>Romagnoli, Giulia ; Offi, Martina ; Capone, Imerio ; Tavilla, Andrea ; Canini, Irene ; Lapenta, Caterina ; Buccarelli, Mariachiara ; Giordano, Martina ; Tirelli, Valentina ; Sanchez, Massimo ; Fragale, Alessandra ; Giannetti, Stefano ; Ceccarelli, Giovanni Maria ; Bonaventura, Rina Di ; Doglietto, Francesco ; Olivi, Alessandro ; Lauretti, Liverana ; Biffoni, Mauro ; Ricci-Vitiani, Lucia ; Pallini, Roberto ; Gabriele, Lucia ; D’Alessandris, Quintino Giorgio</creatorcontrib><description>Abstract BACKGROUND Glioblastoma, IDH-wildtype (GBM), is the most prevalent and aggressive primary brain cancer with a poor prognosis. Immune checkpoint inhibitors (ICIs) have been explored in GBM with limited success, highlighting the need for a better understanding of the tumor microenvironment (TME). This study investigated whether the expression of specific immune checkpoints on tissue-resident memory T cells (Trm) predicts patient outcomes. METHODS In a single cohort observational study, tumor samples from 45 histologically confirmed GBM patients were processed to obtain single-cell suspensions. Multiparametric flow cytometry was used to analyze the correlation of Trm phenotypes with overall survival (OS) and progression-free survival (PFS). Univariate and multivariate analyses were conducted to assess the prognostic significance of Trm subsets. RESULTS Low frequency of exausted Trm expressing programmed cell death protein 1 (PD1) and T cell immunoglobulin and mucin domain-containing protein 3 (TIM3) was associated with better clinical outcomes. Multivariate analysis identified low CD8+CD103+PD1+TIM3+ Trm and Karnofsky performance status (KPS) ≥70 as the most significant independent prognostic factors for longer OS (hazard ratios—HR [95%CI]: 0.14 [0.04–0.52] p &lt; 0.001, 0.39 [0.16–0.96] p = 0.04, respectively). Additionally, younger patients (&lt;63 years) and males had distinct immune profiles affecting prognosis. Notably, the proportion of exausted CD8+CD103+PD1+ Trms had a prognostic correlate only in male patients, consistent with findings by other groups on the existance of gender-specific immune TME in GBM. CONCLUSIONS Further exploration of Trm-based immune profiling has the potential to shed light on GBM resistance to ICIs and to help in personalizing treatment strategies.</description><identifier>ISSN: 1522-8517</identifier><identifier>EISSN: 1523-5866</identifier><identifier>DOI: 10.1093/neuonc/noae165.1206</identifier><language>eng</language><publisher>US: Oxford University Press</publisher><ispartof>Neuro-oncology (Charlottesville, Va.), 2024-11, Vol.26 (Supplement_8), p.viii303-viii304</ispartof><rights>The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. 2024</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids></links><search><creatorcontrib>Romagnoli, Giulia</creatorcontrib><creatorcontrib>Offi, Martina</creatorcontrib><creatorcontrib>Capone, Imerio</creatorcontrib><creatorcontrib>Tavilla, Andrea</creatorcontrib><creatorcontrib>Canini, Irene</creatorcontrib><creatorcontrib>Lapenta, Caterina</creatorcontrib><creatorcontrib>Buccarelli, Mariachiara</creatorcontrib><creatorcontrib>Giordano, Martina</creatorcontrib><creatorcontrib>Tirelli, Valentina</creatorcontrib><creatorcontrib>Sanchez, Massimo</creatorcontrib><creatorcontrib>Fragale, Alessandra</creatorcontrib><creatorcontrib>Giannetti, Stefano</creatorcontrib><creatorcontrib>Ceccarelli, Giovanni Maria</creatorcontrib><creatorcontrib>Bonaventura, Rina Di</creatorcontrib><creatorcontrib>Doglietto, Francesco</creatorcontrib><creatorcontrib>Olivi, Alessandro</creatorcontrib><creatorcontrib>Lauretti, Liverana</creatorcontrib><creatorcontrib>Biffoni, Mauro</creatorcontrib><creatorcontrib>Ricci-Vitiani, Lucia</creatorcontrib><creatorcontrib>Pallini, Roberto</creatorcontrib><creatorcontrib>Gabriele, Lucia</creatorcontrib><creatorcontrib>D’Alessandris, Quintino Giorgio</creatorcontrib><title>TMIC-28. TITLE: AN IMMUNE-RELATED, SEX-SPECIFIC T-CELL SIGNATURE IN GLIOBLASTOMA MICROENVIRONMENT WITH PROGNOSTIC IMPACT</title><title>Neuro-oncology (Charlottesville, Va.)</title><description>Abstract BACKGROUND Glioblastoma, IDH-wildtype (GBM), is the most prevalent and aggressive primary brain cancer with a poor prognosis. Immune checkpoint inhibitors (ICIs) have been explored in GBM with limited success, highlighting the need for a better understanding of the tumor microenvironment (TME). This study investigated whether the expression of specific immune checkpoints on tissue-resident memory T cells (Trm) predicts patient outcomes. METHODS In a single cohort observational study, tumor samples from 45 histologically confirmed GBM patients were processed to obtain single-cell suspensions. Multiparametric flow cytometry was used to analyze the correlation of Trm phenotypes with overall survival (OS) and progression-free survival (PFS). Univariate and multivariate analyses were conducted to assess the prognostic significance of Trm subsets. RESULTS Low frequency of exausted Trm expressing programmed cell death protein 1 (PD1) and T cell immunoglobulin and mucin domain-containing protein 3 (TIM3) was associated with better clinical outcomes. Multivariate analysis identified low CD8+CD103+PD1+TIM3+ Trm and Karnofsky performance status (KPS) ≥70 as the most significant independent prognostic factors for longer OS (hazard ratios—HR [95%CI]: 0.14 [0.04–0.52] p &lt; 0.001, 0.39 [0.16–0.96] p = 0.04, respectively). Additionally, younger patients (&lt;63 years) and males had distinct immune profiles affecting prognosis. Notably, the proportion of exausted CD8+CD103+PD1+ Trms had a prognostic correlate only in male patients, consistent with findings by other groups on the existance of gender-specific immune TME in GBM. CONCLUSIONS Further exploration of Trm-based immune profiling has the potential to shed light on GBM resistance to ICIs and to help in personalizing treatment strategies.</description><issn>1522-8517</issn><issn>1523-5866</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNqNkMFOgzAAhhujiXP6BF76AJa1QEvxhrVjTUoh0Kk3wgokGh0LZIm-vZvbA3j6_8v3HT4A7gn2CI6DxbbbD1u32A5NRxj1iI_ZBZgR6geIcsYu_76POCXRNbiZpg-MfUIZmYFvmymBfO5Bq6yWjzAxUGXZ2khUSp1Y-fwAK_mGqkIKtVQCWiSk1rBSqUnsupRQGZhqlT_ppLJ5lsCDr8yleVFlbjJpLHxVdgWLMk9NXtmDQWVFIuwtuOqbz6m7O-8c2KW0YoV0niqRaOR4wJALHW6ilvas3UTEj3jM4w6HcUhCFkY9i53jrKEtaSj1HY7whvU8wqTtQkpoQ4M5CE5aNw7TNHZ9vRvfv5rxpya4PrarT-3qc7v62O5AeSdq2O_-BfwCB5xqVQ</recordid><startdate>20241111</startdate><enddate>20241111</enddate><creator>Romagnoli, Giulia</creator><creator>Offi, Martina</creator><creator>Capone, Imerio</creator><creator>Tavilla, Andrea</creator><creator>Canini, Irene</creator><creator>Lapenta, Caterina</creator><creator>Buccarelli, Mariachiara</creator><creator>Giordano, Martina</creator><creator>Tirelli, Valentina</creator><creator>Sanchez, Massimo</creator><creator>Fragale, Alessandra</creator><creator>Giannetti, Stefano</creator><creator>Ceccarelli, Giovanni Maria</creator><creator>Bonaventura, Rina Di</creator><creator>Doglietto, Francesco</creator><creator>Olivi, Alessandro</creator><creator>Lauretti, Liverana</creator><creator>Biffoni, Mauro</creator><creator>Ricci-Vitiani, Lucia</creator><creator>Pallini, Roberto</creator><creator>Gabriele, Lucia</creator><creator>D’Alessandris, Quintino Giorgio</creator><general>Oxford University Press</general><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>20241111</creationdate><title>TMIC-28. TITLE: AN IMMUNE-RELATED, SEX-SPECIFIC T-CELL SIGNATURE IN GLIOBLASTOMA MICROENVIRONMENT WITH PROGNOSTIC IMPACT</title><author>Romagnoli, Giulia ; Offi, Martina ; Capone, Imerio ; Tavilla, Andrea ; Canini, Irene ; Lapenta, Caterina ; Buccarelli, Mariachiara ; Giordano, Martina ; Tirelli, Valentina ; Sanchez, Massimo ; Fragale, Alessandra ; Giannetti, Stefano ; Ceccarelli, Giovanni Maria ; Bonaventura, Rina Di ; Doglietto, Francesco ; Olivi, Alessandro ; Lauretti, Liverana ; Biffoni, Mauro ; Ricci-Vitiani, Lucia ; Pallini, Roberto ; Gabriele, Lucia ; D’Alessandris, Quintino Giorgio</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c836-c4c0a7d5f6db71278989e049414647f69cc86a5d1a552c070b6f8701de4515a53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Romagnoli, Giulia</creatorcontrib><creatorcontrib>Offi, Martina</creatorcontrib><creatorcontrib>Capone, Imerio</creatorcontrib><creatorcontrib>Tavilla, Andrea</creatorcontrib><creatorcontrib>Canini, Irene</creatorcontrib><creatorcontrib>Lapenta, Caterina</creatorcontrib><creatorcontrib>Buccarelli, Mariachiara</creatorcontrib><creatorcontrib>Giordano, Martina</creatorcontrib><creatorcontrib>Tirelli, Valentina</creatorcontrib><creatorcontrib>Sanchez, Massimo</creatorcontrib><creatorcontrib>Fragale, Alessandra</creatorcontrib><creatorcontrib>Giannetti, Stefano</creatorcontrib><creatorcontrib>Ceccarelli, Giovanni Maria</creatorcontrib><creatorcontrib>Bonaventura, Rina Di</creatorcontrib><creatorcontrib>Doglietto, Francesco</creatorcontrib><creatorcontrib>Olivi, Alessandro</creatorcontrib><creatorcontrib>Lauretti, Liverana</creatorcontrib><creatorcontrib>Biffoni, Mauro</creatorcontrib><creatorcontrib>Ricci-Vitiani, Lucia</creatorcontrib><creatorcontrib>Pallini, Roberto</creatorcontrib><creatorcontrib>Gabriele, Lucia</creatorcontrib><creatorcontrib>D’Alessandris, Quintino Giorgio</creatorcontrib><collection>CrossRef</collection><jtitle>Neuro-oncology (Charlottesville, Va.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Romagnoli, Giulia</au><au>Offi, Martina</au><au>Capone, Imerio</au><au>Tavilla, Andrea</au><au>Canini, Irene</au><au>Lapenta, Caterina</au><au>Buccarelli, Mariachiara</au><au>Giordano, Martina</au><au>Tirelli, Valentina</au><au>Sanchez, Massimo</au><au>Fragale, Alessandra</au><au>Giannetti, Stefano</au><au>Ceccarelli, Giovanni Maria</au><au>Bonaventura, Rina Di</au><au>Doglietto, Francesco</au><au>Olivi, Alessandro</au><au>Lauretti, Liverana</au><au>Biffoni, Mauro</au><au>Ricci-Vitiani, Lucia</au><au>Pallini, Roberto</au><au>Gabriele, Lucia</au><au>D’Alessandris, Quintino Giorgio</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>TMIC-28. TITLE: AN IMMUNE-RELATED, SEX-SPECIFIC T-CELL SIGNATURE IN GLIOBLASTOMA MICROENVIRONMENT WITH PROGNOSTIC IMPACT</atitle><jtitle>Neuro-oncology (Charlottesville, Va.)</jtitle><date>2024-11-11</date><risdate>2024</risdate><volume>26</volume><issue>Supplement_8</issue><spage>viii303</spage><epage>viii304</epage><pages>viii303-viii304</pages><issn>1522-8517</issn><eissn>1523-5866</eissn><abstract>Abstract BACKGROUND Glioblastoma, IDH-wildtype (GBM), is the most prevalent and aggressive primary brain cancer with a poor prognosis. Immune checkpoint inhibitors (ICIs) have been explored in GBM with limited success, highlighting the need for a better understanding of the tumor microenvironment (TME). This study investigated whether the expression of specific immune checkpoints on tissue-resident memory T cells (Trm) predicts patient outcomes. METHODS In a single cohort observational study, tumor samples from 45 histologically confirmed GBM patients were processed to obtain single-cell suspensions. Multiparametric flow cytometry was used to analyze the correlation of Trm phenotypes with overall survival (OS) and progression-free survival (PFS). Univariate and multivariate analyses were conducted to assess the prognostic significance of Trm subsets. RESULTS Low frequency of exausted Trm expressing programmed cell death protein 1 (PD1) and T cell immunoglobulin and mucin domain-containing protein 3 (TIM3) was associated with better clinical outcomes. Multivariate analysis identified low CD8+CD103+PD1+TIM3+ Trm and Karnofsky performance status (KPS) ≥70 as the most significant independent prognostic factors for longer OS (hazard ratios—HR [95%CI]: 0.14 [0.04–0.52] p &lt; 0.001, 0.39 [0.16–0.96] p = 0.04, respectively). Additionally, younger patients (&lt;63 years) and males had distinct immune profiles affecting prognosis. Notably, the proportion of exausted CD8+CD103+PD1+ Trms had a prognostic correlate only in male patients, consistent with findings by other groups on the existance of gender-specific immune TME in GBM. CONCLUSIONS Further exploration of Trm-based immune profiling has the potential to shed light on GBM resistance to ICIs and to help in personalizing treatment strategies.</abstract><cop>US</cop><pub>Oxford University Press</pub><doi>10.1093/neuonc/noae165.1206</doi></addata></record>
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source Oxford University Press Journals All Titles (1996-Current)
title TMIC-28. TITLE: AN IMMUNE-RELATED, SEX-SPECIFIC T-CELL SIGNATURE IN GLIOBLASTOMA MICROENVIRONMENT WITH PROGNOSTIC IMPACT
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