Integrative immune transcriptomic classification improves patient selection for precision immunotherapy in advanced gastro-oesophageal adenocarcinoma
Background Advanced gastro-oesophageal cancer (GEA) treatment has been improved by the introduction of immune checkpoint inhibitors (CPIs), yet identifying predictive biomarkers remains a priority, particularly in patients with a combined positive score (CPS)
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| Veröffentlicht in: | British journal of cancer 2022-12, Vol.127 (12), p.2198-2206 |
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| creator | Cabeza-Segura, Manuel Gambardella, Valentina Gimeno-Valiente, Francisco Carbonell-Asins, Juan Antonio Alarcón-Molero, Lorena González-Vilanova, Arturo Zuñiga-Trejos, Sheila Rentero-Garrido, Pilar Villagrasa, Rosana Gil, Mireia Durá, Ana Richart, Paula Alonso, Noelia Huerta, Marisol Roselló, Susana Roda, Desamparados Tarazona, Noelia Martínez-Ciarpaglini, Carolina Castillo, Josefa Cervantes, Andrés Fleitas, Tania |
| description | Background
Advanced gastro-oesophageal cancer (GEA) treatment has been improved by the introduction of immune checkpoint inhibitors (CPIs), yet identifying predictive biomarkers remains a priority, particularly in patients with a combined positive score (CPS) |
| doi_str_mv | 10.1038/s41416-022-02005-z |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_9727124</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2725654119</sourcerecordid><originalsourceid>FETCH-LOGICAL-c474t-318fdc99eb8c53b0a8c0fc2c86c3b4d60cb3bbf66e764923c624cec1b0cd3fa03</originalsourceid><addsrcrecordid>eNp9kc1u1TAQhS0EopfCC7BAkdiwCfgvfxskVAGtVIlNu7acySTXVWIHO7lS-x68b6dNKZQFC9sanW_OeHQYeyv4R8FV_SlpoUWZcynpcF7kN8_YThRK5qKW1XO245xXOW8kP2KvUrqisuF19ZIdqVIWqpBqx36d-QWHaBd3wMxN0-oxW6L1CaKblzA5yGC0KbneAUHBEzTHcMCUzVSjX7KEI8K91IeYzRHBpQ0kt7DsMdr5OnM-s93BesAuG2xaYsgDpjDv7YB2JA19ABvB-TDZ1-xFb8eEbx7eY3b57evFyWl-_uP72cmX8xx0pZdcibrvoGmwraFQLbc18B4k1CWoVnclh1a1bV-WWJW6kQpKqQFBtBw61VuujtnnzXde2wk7oHWiHc0c3WTjtQnWmaeKd3szhINpKlkJqcngw4NBDD9XTIuZXAIcR-sxrMnIShZloYVoCH3_D3oV1uhpPaI0udGliJIbBTGkFLF__Izg5i51s6VuKHVzn7q5oaZ3f6_x2PI7ZgLUBiSS_IDxz-z_2N4C9uC_vw</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2747127473</pqid></control><display><type>article</type><title>Integrative immune transcriptomic classification improves patient selection for precision immunotherapy in advanced gastro-oesophageal adenocarcinoma</title><source>MEDLINE</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><source>SpringerLink Journals - AutoHoldings</source><creator>Cabeza-Segura, Manuel ; Gambardella, Valentina ; Gimeno-Valiente, Francisco ; Carbonell-Asins, Juan Antonio ; Alarcón-Molero, Lorena ; González-Vilanova, Arturo ; Zuñiga-Trejos, Sheila ; Rentero-Garrido, Pilar ; Villagrasa, Rosana ; Gil, Mireia ; Durá, Ana ; Richart, Paula ; Alonso, Noelia ; Huerta, Marisol ; Roselló, Susana ; Roda, Desamparados ; Tarazona, Noelia ; Martínez-Ciarpaglini, Carolina ; Castillo, Josefa ; Cervantes, Andrés ; Fleitas, Tania</creator><creatorcontrib>Cabeza-Segura, Manuel ; Gambardella, Valentina ; Gimeno-Valiente, Francisco ; Carbonell-Asins, Juan Antonio ; Alarcón-Molero, Lorena ; González-Vilanova, Arturo ; Zuñiga-Trejos, Sheila ; Rentero-Garrido, Pilar ; Villagrasa, Rosana ; Gil, Mireia ; Durá, Ana ; Richart, Paula ; Alonso, Noelia ; Huerta, Marisol ; Roselló, Susana ; Roda, Desamparados ; Tarazona, Noelia ; Martínez-Ciarpaglini, Carolina ; Castillo, Josefa ; Cervantes, Andrés ; Fleitas, Tania</creatorcontrib><description>Background
Advanced gastro-oesophageal cancer (GEA) treatment has been improved by the introduction of immune checkpoint inhibitors (CPIs), yet identifying predictive biomarkers remains a priority, particularly in patients with a combined positive score (CPS) < 5, where the benefit is less clear. Our study assesses certain immune microenvironment features related to sensitivity or resistance to CPIs with the aim of implementing a personalised approach across CPS < 5 GEA.
Design
Through integrative transcriptomic and clinicopathological analyses, we studied in both a retrospective and a prospective cohort, the immune tumour microenvironment features. We analysed the cell types composing the immune infiltrate highlighting their functional activity.
Results
This integrative study allowed the identification of four different groups across our patients. Among them, we identified a cluster whose tumours expressed the most gene signatures related to immunomodulatory pathways and immunotherapy response. These tumours presented an enriched immune infiltrate showing high immune function activity that could potentially achieve the best benefit from CPIs. Finally, our findings were proven in an external CPI-exposed population, where the use of our transcriptomic results combined with CPS helped better identify those patients who could benefit from immunotherapy than using CPS alone (
p
= 0.043).
Conclusions
This transcriptomic classification could improve precision immunotherapy for GEA.</description><identifier>ISSN: 0007-0920</identifier><identifier>EISSN: 1532-1827</identifier><identifier>DOI: 10.1038/s41416-022-02005-z</identifier><identifier>PMID: 36253523</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>692/4028/67/1504/1829 ; 692/4028/67/327 ; Adenocarcinoma ; Biomedical and Life Sciences ; Biomedicine ; Cancer Research ; Drug Resistance ; Epidemiology ; Esophageal cancer ; Esophageal Neoplasms - genetics ; Esophageal Neoplasms - therapy ; Humans ; Immune checkpoint inhibitors ; Immune response ; Immunomodulation ; Immunotherapy ; Microenvironments ; Molecular Medicine ; Oncology ; Patient Selection ; Patients ; Prospective Studies ; Retrospective Studies ; Transcriptomics ; Tumor microenvironment ; Tumor Microenvironment - genetics ; Tumors</subject><ispartof>British journal of cancer, 2022-12, Vol.127 (12), p.2198-2206</ispartof><rights>The Author(s) 2022</rights><rights>2022. The Author(s).</rights><rights>The Author(s) 2022. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-318fdc99eb8c53b0a8c0fc2c86c3b4d60cb3bbf66e764923c624cec1b0cd3fa03</citedby><cites>FETCH-LOGICAL-c474t-318fdc99eb8c53b0a8c0fc2c86c3b4d60cb3bbf66e764923c624cec1b0cd3fa03</cites><orcidid>0000-0003-3806-3691 ; 0000-0002-2789-9082</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9727124/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9727124/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27923,27924,41487,42556,51318,53790,53792</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36253523$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cabeza-Segura, Manuel</creatorcontrib><creatorcontrib>Gambardella, Valentina</creatorcontrib><creatorcontrib>Gimeno-Valiente, Francisco</creatorcontrib><creatorcontrib>Carbonell-Asins, Juan Antonio</creatorcontrib><creatorcontrib>Alarcón-Molero, Lorena</creatorcontrib><creatorcontrib>González-Vilanova, Arturo</creatorcontrib><creatorcontrib>Zuñiga-Trejos, Sheila</creatorcontrib><creatorcontrib>Rentero-Garrido, Pilar</creatorcontrib><creatorcontrib>Villagrasa, Rosana</creatorcontrib><creatorcontrib>Gil, Mireia</creatorcontrib><creatorcontrib>Durá, Ana</creatorcontrib><creatorcontrib>Richart, Paula</creatorcontrib><creatorcontrib>Alonso, Noelia</creatorcontrib><creatorcontrib>Huerta, Marisol</creatorcontrib><creatorcontrib>Roselló, Susana</creatorcontrib><creatorcontrib>Roda, Desamparados</creatorcontrib><creatorcontrib>Tarazona, Noelia</creatorcontrib><creatorcontrib>Martínez-Ciarpaglini, Carolina</creatorcontrib><creatorcontrib>Castillo, Josefa</creatorcontrib><creatorcontrib>Cervantes, Andrés</creatorcontrib><creatorcontrib>Fleitas, Tania</creatorcontrib><title>Integrative immune transcriptomic classification improves patient selection for precision immunotherapy in advanced gastro-oesophageal adenocarcinoma</title><title>British journal of cancer</title><addtitle>Br J Cancer</addtitle><addtitle>Br J Cancer</addtitle><description>Background
Advanced gastro-oesophageal cancer (GEA) treatment has been improved by the introduction of immune checkpoint inhibitors (CPIs), yet identifying predictive biomarkers remains a priority, particularly in patients with a combined positive score (CPS) < 5, where the benefit is less clear. Our study assesses certain immune microenvironment features related to sensitivity or resistance to CPIs with the aim of implementing a personalised approach across CPS < 5 GEA.
Design
Through integrative transcriptomic and clinicopathological analyses, we studied in both a retrospective and a prospective cohort, the immune tumour microenvironment features. We analysed the cell types composing the immune infiltrate highlighting their functional activity.
Results
This integrative study allowed the identification of four different groups across our patients. Among them, we identified a cluster whose tumours expressed the most gene signatures related to immunomodulatory pathways and immunotherapy response. These tumours presented an enriched immune infiltrate showing high immune function activity that could potentially achieve the best benefit from CPIs. Finally, our findings were proven in an external CPI-exposed population, where the use of our transcriptomic results combined with CPS helped better identify those patients who could benefit from immunotherapy than using CPS alone (
p
= 0.043).
Conclusions
This transcriptomic classification could improve precision immunotherapy for GEA.</description><subject>692/4028/67/1504/1829</subject><subject>692/4028/67/327</subject><subject>Adenocarcinoma</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer Research</subject><subject>Drug Resistance</subject><subject>Epidemiology</subject><subject>Esophageal cancer</subject><subject>Esophageal Neoplasms - genetics</subject><subject>Esophageal Neoplasms - therapy</subject><subject>Humans</subject><subject>Immune checkpoint inhibitors</subject><subject>Immune response</subject><subject>Immunomodulation</subject><subject>Immunotherapy</subject><subject>Microenvironments</subject><subject>Molecular Medicine</subject><subject>Oncology</subject><subject>Patient Selection</subject><subject>Patients</subject><subject>Prospective Studies</subject><subject>Retrospective Studies</subject><subject>Transcriptomics</subject><subject>Tumor microenvironment</subject><subject>Tumor Microenvironment - 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genetics</topic><topic>Esophageal Neoplasms - therapy</topic><topic>Humans</topic><topic>Immune checkpoint inhibitors</topic><topic>Immune response</topic><topic>Immunomodulation</topic><topic>Immunotherapy</topic><topic>Microenvironments</topic><topic>Molecular Medicine</topic><topic>Oncology</topic><topic>Patient Selection</topic><topic>Patients</topic><topic>Prospective Studies</topic><topic>Retrospective Studies</topic><topic>Transcriptomics</topic><topic>Tumor microenvironment</topic><topic>Tumor Microenvironment - genetics</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cabeza-Segura, Manuel</creatorcontrib><creatorcontrib>Gambardella, Valentina</creatorcontrib><creatorcontrib>Gimeno-Valiente, Francisco</creatorcontrib><creatorcontrib>Carbonell-Asins, Juan Antonio</creatorcontrib><creatorcontrib>Alarcón-Molero, Lorena</creatorcontrib><creatorcontrib>González-Vilanova, Arturo</creatorcontrib><creatorcontrib>Zuñiga-Trejos, Sheila</creatorcontrib><creatorcontrib>Rentero-Garrido, Pilar</creatorcontrib><creatorcontrib>Villagrasa, Rosana</creatorcontrib><creatorcontrib>Gil, Mireia</creatorcontrib><creatorcontrib>Durá, Ana</creatorcontrib><creatorcontrib>Richart, Paula</creatorcontrib><creatorcontrib>Alonso, Noelia</creatorcontrib><creatorcontrib>Huerta, Marisol</creatorcontrib><creatorcontrib>Roselló, Susana</creatorcontrib><creatorcontrib>Roda, Desamparados</creatorcontrib><creatorcontrib>Tarazona, Noelia</creatorcontrib><creatorcontrib>Martínez-Ciarpaglini, Carolina</creatorcontrib><creatorcontrib>Castillo, Josefa</creatorcontrib><creatorcontrib>Cervantes, Andrés</creatorcontrib><creatorcontrib>Fleitas, Tania</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>British Nursing Database</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection (ProQuest)</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>British journal of cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cabeza-Segura, Manuel</au><au>Gambardella, Valentina</au><au>Gimeno-Valiente, Francisco</au><au>Carbonell-Asins, Juan Antonio</au><au>Alarcón-Molero, Lorena</au><au>González-Vilanova, Arturo</au><au>Zuñiga-Trejos, Sheila</au><au>Rentero-Garrido, Pilar</au><au>Villagrasa, Rosana</au><au>Gil, Mireia</au><au>Durá, Ana</au><au>Richart, Paula</au><au>Alonso, Noelia</au><au>Huerta, Marisol</au><au>Roselló, Susana</au><au>Roda, Desamparados</au><au>Tarazona, Noelia</au><au>Martínez-Ciarpaglini, Carolina</au><au>Castillo, Josefa</au><au>Cervantes, Andrés</au><au>Fleitas, Tania</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Integrative immune transcriptomic classification improves patient selection for precision immunotherapy in advanced gastro-oesophageal adenocarcinoma</atitle><jtitle>British journal of cancer</jtitle><stitle>Br J Cancer</stitle><addtitle>Br J Cancer</addtitle><date>2022-12-07</date><risdate>2022</risdate><volume>127</volume><issue>12</issue><spage>2198</spage><epage>2206</epage><pages>2198-2206</pages><issn>0007-0920</issn><eissn>1532-1827</eissn><abstract>Background
Advanced gastro-oesophageal cancer (GEA) treatment has been improved by the introduction of immune checkpoint inhibitors (CPIs), yet identifying predictive biomarkers remains a priority, particularly in patients with a combined positive score (CPS) < 5, where the benefit is less clear. Our study assesses certain immune microenvironment features related to sensitivity or resistance to CPIs with the aim of implementing a personalised approach across CPS < 5 GEA.
Design
Through integrative transcriptomic and clinicopathological analyses, we studied in both a retrospective and a prospective cohort, the immune tumour microenvironment features. We analysed the cell types composing the immune infiltrate highlighting their functional activity.
Results
This integrative study allowed the identification of four different groups across our patients. Among them, we identified a cluster whose tumours expressed the most gene signatures related to immunomodulatory pathways and immunotherapy response. These tumours presented an enriched immune infiltrate showing high immune function activity that could potentially achieve the best benefit from CPIs. Finally, our findings were proven in an external CPI-exposed population, where the use of our transcriptomic results combined with CPS helped better identify those patients who could benefit from immunotherapy than using CPS alone (
p
= 0.043).
Conclusions
This transcriptomic classification could improve precision immunotherapy for GEA.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>36253523</pmid><doi>10.1038/s41416-022-02005-z</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0003-3806-3691</orcidid><orcidid>https://orcid.org/0000-0002-2789-9082</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | British journal of cancer, 2022-12, Vol.127 (12), p.2198-2206 |
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| language | eng |
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| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; PubMed Central; SpringerLink Journals - AutoHoldings |
| subjects | 692/4028/67/1504/1829 692/4028/67/327 Adenocarcinoma Biomedical and Life Sciences Biomedicine Cancer Research Drug Resistance Epidemiology Esophageal cancer Esophageal Neoplasms - genetics Esophageal Neoplasms - therapy Humans Immune checkpoint inhibitors Immune response Immunomodulation Immunotherapy Microenvironments Molecular Medicine Oncology Patient Selection Patients Prospective Studies Retrospective Studies Transcriptomics Tumor microenvironment Tumor Microenvironment - genetics Tumors |
| title | Integrative immune transcriptomic classification improves patient selection for precision immunotherapy in advanced gastro-oesophageal adenocarcinoma |
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