An investigation of the clinical impact and therapeutic relevance of a DNA damage immune response (DDIR) signature in patients with advanced gastroesophageal adenocarcinoma
An improved understanding of which gastroesophageal adenocarcinoma (GOA) patients respond to both chemotherapy and immune checkpoint inhibitors (ICI) is needed. We investigated the predictive role and underlying biology of a 44-gene DNA damage immune response (DDIR) signature in patients with advanc...
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| creator | Baxter, M.A. Spender, L.C. Cairns, D. Walsh, S. Oparka, R. Porter, R.J. Bray, S. Skinner, G. King, S. Turbitt, J. Collinson, D. Miedzybrodzka, Z.H. Jellema, G. Logan, G. Kennedy, R.D. Turkington, R.C. McLean, M.H. Swinson, D. Grabsch, H.I. Lord, S. Seymour, M.J. Hall, P.S. Petty, R.D. |
| description | An improved understanding of which gastroesophageal adenocarcinoma (GOA) patients respond to both chemotherapy and immune checkpoint inhibitors (ICI) is needed. We investigated the predictive role and underlying biology of a 44-gene DNA damage immune response (DDIR) signature in patients with advanced GOA.
Transcriptional profiling was carried out on pretreatment tissue from 252 GOA patients treated with platinum-based chemotherapy (three dose levels) within the randomized phase III GO2 trial. Cross-validation was carried out in two independent GOA cohorts with transcriptional profiling, immune cell immunohistochemistry and epidermal growth factor receptor (EGFR) fluorescent in situ hybridization (FISH) (n = 430).
In the GO2 trial, DDIR-positive tumours had a greater radiological response (51.7% versus 28.5%, P = 0.022) and improved overall survival in a dose-dependent manner (P = 0.028). DDIR positivity was associated with a pretreatment inflamed tumour microenvironment (TME) and increased expression of biomarkers associated with ICI response such as CD274 (programmed death-ligand 1, PD-L1) and a microsatellite instability RNA signature. Consensus pathway analysis identified EGFR as a potential key determinant of the DDIR signature. EGFR amplification was associated with DDIR negativity and an immune cold TME.
Our results indicate the importance of the GOA TME in chemotherapy response, its relationship to DNA damage repair and EGFR as a targetable driver of an immune cold TME. Chemotherapy-sensitive inflamed GOAs could benefit from ICI delivered in combination with standard chemotherapy. Combining EGFR inhibitors and ICIs warrants further investigation in patients with EGFR-amplified tumours.
•The DDIR signature is predictive of chemotherapy response and dose-dependent survival in gastroesophageal adenocarcinoma.•DDIR-positive tumours have an immune hot tumour microenvironment with expression of biomarkers of immunotherapy response.•Epidermal growth factor receptor (EGFR) is identified as a potential driver of an immune cold tumour microenvironment. |
| doi_str_mv | 10.1016/j.esmoop.2024.103450 |
| format | Article |
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Transcriptional profiling was carried out on pretreatment tissue from 252 GOA patients treated with platinum-based chemotherapy (three dose levels) within the randomized phase III GO2 trial. Cross-validation was carried out in two independent GOA cohorts with transcriptional profiling, immune cell immunohistochemistry and epidermal growth factor receptor (EGFR) fluorescent in situ hybridization (FISH) (n = 430).
In the GO2 trial, DDIR-positive tumours had a greater radiological response (51.7% versus 28.5%, P = 0.022) and improved overall survival in a dose-dependent manner (P = 0.028). DDIR positivity was associated with a pretreatment inflamed tumour microenvironment (TME) and increased expression of biomarkers associated with ICI response such as CD274 (programmed death-ligand 1, PD-L1) and a microsatellite instability RNA signature. Consensus pathway analysis identified EGFR as a potential key determinant of the DDIR signature. EGFR amplification was associated with DDIR negativity and an immune cold TME.
Our results indicate the importance of the GOA TME in chemotherapy response, its relationship to DNA damage repair and EGFR as a targetable driver of an immune cold TME. Chemotherapy-sensitive inflamed GOAs could benefit from ICI delivered in combination with standard chemotherapy. Combining EGFR inhibitors and ICIs warrants further investigation in patients with EGFR-amplified tumours.
•The DDIR signature is predictive of chemotherapy response and dose-dependent survival in gastroesophageal adenocarcinoma.•DDIR-positive tumours have an immune hot tumour microenvironment with expression of biomarkers of immunotherapy response.•Epidermal growth factor receptor (EGFR) is identified as a potential driver of an immune cold tumour microenvironment.</description><identifier>ISSN: 2059-7029</identifier><identifier>EISSN: 2059-7029</identifier><identifier>DOI: 10.1016/j.esmoop.2024.103450</identifier><identifier>PMID: 38744099</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Adenocarcinoma - drug therapy ; Adenocarcinoma - genetics ; Adenocarcinoma - immunology ; Aged ; Biomarkers, Tumor - metabolism ; DNA Damage ; DNA damage immune response ; epidermal growth factor receptor ; ErbB Receptors - metabolism ; Esophageal Neoplasms - drug therapy ; Esophageal Neoplasms - genetics ; Esophageal Neoplasms - immunology ; Female ; gastroesophageal adenocarcinoma ; Humans ; immune checkpoint inhibitors ; Immune Checkpoint Inhibitors - pharmacology ; Immune Checkpoint Inhibitors - therapeutic use ; Male ; Middle Aged ; Original Research ; Stomach Neoplasms - drug therapy ; Stomach Neoplasms - genetics ; Stomach Neoplasms - immunology ; Tumor Microenvironment - immunology ; tumour microenvironment</subject><ispartof>ESMO open, 2024-05, Vol.9 (5), p.103450, Article 103450</ispartof><rights>2024 The Authors</rights><rights>Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.</rights><rights>2024 The Authors 2024</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c413t-7851f6d1f7ac8e8ca4cf80bf44d5c61e78892a6fd0e528fff37bde7ff5a3c6e83</cites><orcidid>0000-0003-3164-1890 ; 0000-0002-5773-8650 ; 0000-0002-7443-2653 ; 0000-0001-7946-5609 ; 0000-0002-2338-0179 ; 0000-0002-2441-9629 ; 0009-0005-2936-6828 ; 0000-0003-4737-6163</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/PMC11108838/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11108838/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,724,777,781,882,27905,27906,53772,53774</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38744099$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Baxter, M.A.</creatorcontrib><creatorcontrib>Spender, L.C.</creatorcontrib><creatorcontrib>Cairns, D.</creatorcontrib><creatorcontrib>Walsh, S.</creatorcontrib><creatorcontrib>Oparka, R.</creatorcontrib><creatorcontrib>Porter, R.J.</creatorcontrib><creatorcontrib>Bray, S.</creatorcontrib><creatorcontrib>Skinner, G.</creatorcontrib><creatorcontrib>King, S.</creatorcontrib><creatorcontrib>Turbitt, J.</creatorcontrib><creatorcontrib>Collinson, D.</creatorcontrib><creatorcontrib>Miedzybrodzka, Z.H.</creatorcontrib><creatorcontrib>Jellema, G.</creatorcontrib><creatorcontrib>Logan, G.</creatorcontrib><creatorcontrib>Kennedy, R.D.</creatorcontrib><creatorcontrib>Turkington, R.C.</creatorcontrib><creatorcontrib>McLean, M.H.</creatorcontrib><creatorcontrib>Swinson, D.</creatorcontrib><creatorcontrib>Grabsch, H.I.</creatorcontrib><creatorcontrib>Lord, S.</creatorcontrib><creatorcontrib>Seymour, M.J.</creatorcontrib><creatorcontrib>Hall, P.S.</creatorcontrib><creatorcontrib>Petty, R.D.</creatorcontrib><title>An investigation of the clinical impact and therapeutic relevance of a DNA damage immune response (DDIR) signature in patients with advanced gastroesophageal adenocarcinoma</title><title>ESMO open</title><addtitle>ESMO Open</addtitle><description>An improved understanding of which gastroesophageal adenocarcinoma (GOA) patients respond to both chemotherapy and immune checkpoint inhibitors (ICI) is needed. We investigated the predictive role and underlying biology of a 44-gene DNA damage immune response (DDIR) signature in patients with advanced GOA.
Transcriptional profiling was carried out on pretreatment tissue from 252 GOA patients treated with platinum-based chemotherapy (three dose levels) within the randomized phase III GO2 trial. Cross-validation was carried out in two independent GOA cohorts with transcriptional profiling, immune cell immunohistochemistry and epidermal growth factor receptor (EGFR) fluorescent in situ hybridization (FISH) (n = 430).
In the GO2 trial, DDIR-positive tumours had a greater radiological response (51.7% versus 28.5%, P = 0.022) and improved overall survival in a dose-dependent manner (P = 0.028). DDIR positivity was associated with a pretreatment inflamed tumour microenvironment (TME) and increased expression of biomarkers associated with ICI response such as CD274 (programmed death-ligand 1, PD-L1) and a microsatellite instability RNA signature. Consensus pathway analysis identified EGFR as a potential key determinant of the DDIR signature. EGFR amplification was associated with DDIR negativity and an immune cold TME.
Our results indicate the importance of the GOA TME in chemotherapy response, its relationship to DNA damage repair and EGFR as a targetable driver of an immune cold TME. Chemotherapy-sensitive inflamed GOAs could benefit from ICI delivered in combination with standard chemotherapy. Combining EGFR inhibitors and ICIs warrants further investigation in patients with EGFR-amplified tumours.
•The DDIR signature is predictive of chemotherapy response and dose-dependent survival in gastroesophageal adenocarcinoma.•DDIR-positive tumours have an immune hot tumour microenvironment with expression of biomarkers of immunotherapy response.•Epidermal growth factor receptor (EGFR) is identified as a potential driver of an immune cold tumour microenvironment.</description><subject>Adenocarcinoma - drug therapy</subject><subject>Adenocarcinoma - genetics</subject><subject>Adenocarcinoma - immunology</subject><subject>Aged</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>DNA Damage</subject><subject>DNA damage immune response</subject><subject>epidermal growth factor receptor</subject><subject>ErbB Receptors - metabolism</subject><subject>Esophageal Neoplasms - drug therapy</subject><subject>Esophageal Neoplasms - genetics</subject><subject>Esophageal Neoplasms - immunology</subject><subject>Female</subject><subject>gastroesophageal adenocarcinoma</subject><subject>Humans</subject><subject>immune checkpoint inhibitors</subject><subject>Immune Checkpoint Inhibitors - pharmacology</subject><subject>Immune Checkpoint Inhibitors - therapeutic use</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Original Research</subject><subject>Stomach Neoplasms - drug therapy</subject><subject>Stomach Neoplasms - genetics</subject><subject>Stomach Neoplasms - immunology</subject><subject>Tumor Microenvironment - immunology</subject><subject>tumour microenvironment</subject><issn>2059-7029</issn><issn>2059-7029</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9Uctu1DAUjRCIVqV_gJCXZTGDnTiJZwMadXhUqkBCsLbu2NcZjxI72M5U_BMfiUNKVTasbN17HlfnFMVLRteMsubNcY1x8H5cl7TkeVTxmj4pzktab1YtLTdPH_3PissYj5RS1vI8bJ4XZ5VoOaebzXnxa-uIdSeMyXaQrHfEG5IOSFRvnVXQEzuMoBIBp-d5gBGnZBUJ2OMJnMKZAGT3eUs0DNBhJgyTwwyIo3cRydVud_P1NYm2c5CmkAGOjNkLXYrkzqYDAf1HSZMOYgoeox8PWSmbg0bnFQRlnR_gRfHMQB_x8v69KL5_eP_t-tPq9svHm-vt7UpxVqVVK2pmGs1MC0qgUMCVEXRvONe1ahi2QmxKaIymWJfCGFO1e42tMTVUqkFRXRTvFt1x2g-oVb40QC_HYAcIP6UHK__dOHuQnT9JxhgVopoVru4Vgv8x5XTlYKPCvgeHfoqyonXNa9aINkP5AlXBxxjQPPgwKuey5VEuZcu5bLmUnWmvHt_4QPpbbQa8XQCYkzpZDDKqnHmO2QZUSWpv_-_wGyi4wnM</recordid><startdate>20240501</startdate><enddate>20240501</enddate><creator>Baxter, M.A.</creator><creator>Spender, L.C.</creator><creator>Cairns, D.</creator><creator>Walsh, S.</creator><creator>Oparka, R.</creator><creator>Porter, R.J.</creator><creator>Bray, S.</creator><creator>Skinner, G.</creator><creator>King, S.</creator><creator>Turbitt, J.</creator><creator>Collinson, D.</creator><creator>Miedzybrodzka, Z.H.</creator><creator>Jellema, G.</creator><creator>Logan, G.</creator><creator>Kennedy, R.D.</creator><creator>Turkington, R.C.</creator><creator>McLean, M.H.</creator><creator>Swinson, D.</creator><creator>Grabsch, H.I.</creator><creator>Lord, S.</creator><creator>Seymour, M.J.</creator><creator>Hall, P.S.</creator><creator>Petty, R.D.</creator><general>Elsevier Ltd</general><general>Elsevier</general><scope>6I.</scope><scope>AAFTH</scope><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><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-3164-1890</orcidid><orcidid>https://orcid.org/0000-0002-5773-8650</orcidid><orcidid>https://orcid.org/0000-0002-7443-2653</orcidid><orcidid>https://orcid.org/0000-0001-7946-5609</orcidid><orcidid>https://orcid.org/0000-0002-2338-0179</orcidid><orcidid>https://orcid.org/0000-0002-2441-9629</orcidid><orcidid>https://orcid.org/0009-0005-2936-6828</orcidid><orcidid>https://orcid.org/0000-0003-4737-6163</orcidid></search><sort><creationdate>20240501</creationdate><title>An investigation of the clinical impact and therapeutic relevance of a DNA damage immune response (DDIR) signature in patients with advanced gastroesophageal adenocarcinoma</title><author>Baxter, M.A. ; Spender, L.C. ; Cairns, D. ; Walsh, S. ; Oparka, R. ; Porter, R.J. ; Bray, S. ; Skinner, G. ; King, S. ; Turbitt, J. ; Collinson, D. ; Miedzybrodzka, Z.H. ; Jellema, G. ; Logan, G. ; Kennedy, R.D. ; Turkington, R.C. ; McLean, M.H. ; Swinson, D. ; Grabsch, H.I. ; Lord, S. ; Seymour, M.J. ; Hall, P.S. ; Petty, R.D.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c413t-7851f6d1f7ac8e8ca4cf80bf44d5c61e78892a6fd0e528fff37bde7ff5a3c6e83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Adenocarcinoma - drug therapy</topic><topic>Adenocarcinoma - genetics</topic><topic>Adenocarcinoma - immunology</topic><topic>Aged</topic><topic>Biomarkers, Tumor - metabolism</topic><topic>DNA Damage</topic><topic>DNA damage immune response</topic><topic>epidermal growth factor receptor</topic><topic>ErbB Receptors - metabolism</topic><topic>Esophageal Neoplasms - drug therapy</topic><topic>Esophageal Neoplasms - genetics</topic><topic>Esophageal Neoplasms - immunology</topic><topic>Female</topic><topic>gastroesophageal adenocarcinoma</topic><topic>Humans</topic><topic>immune checkpoint inhibitors</topic><topic>Immune Checkpoint Inhibitors - pharmacology</topic><topic>Immune Checkpoint Inhibitors - therapeutic use</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Original Research</topic><topic>Stomach Neoplasms - drug therapy</topic><topic>Stomach Neoplasms - genetics</topic><topic>Stomach Neoplasms - immunology</topic><topic>Tumor Microenvironment - immunology</topic><topic>tumour microenvironment</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Baxter, M.A.</creatorcontrib><creatorcontrib>Spender, L.C.</creatorcontrib><creatorcontrib>Cairns, D.</creatorcontrib><creatorcontrib>Walsh, S.</creatorcontrib><creatorcontrib>Oparka, R.</creatorcontrib><creatorcontrib>Porter, R.J.</creatorcontrib><creatorcontrib>Bray, S.</creatorcontrib><creatorcontrib>Skinner, G.</creatorcontrib><creatorcontrib>King, S.</creatorcontrib><creatorcontrib>Turbitt, J.</creatorcontrib><creatorcontrib>Collinson, D.</creatorcontrib><creatorcontrib>Miedzybrodzka, Z.H.</creatorcontrib><creatorcontrib>Jellema, G.</creatorcontrib><creatorcontrib>Logan, G.</creatorcontrib><creatorcontrib>Kennedy, R.D.</creatorcontrib><creatorcontrib>Turkington, R.C.</creatorcontrib><creatorcontrib>McLean, M.H.</creatorcontrib><creatorcontrib>Swinson, D.</creatorcontrib><creatorcontrib>Grabsch, H.I.</creatorcontrib><creatorcontrib>Lord, S.</creatorcontrib><creatorcontrib>Seymour, M.J.</creatorcontrib><creatorcontrib>Hall, P.S.</creatorcontrib><creatorcontrib>Petty, R.D.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><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><collection>PubMed Central (Full Participant titles)</collection><jtitle>ESMO open</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Baxter, M.A.</au><au>Spender, L.C.</au><au>Cairns, D.</au><au>Walsh, S.</au><au>Oparka, R.</au><au>Porter, R.J.</au><au>Bray, S.</au><au>Skinner, G.</au><au>King, S.</au><au>Turbitt, J.</au><au>Collinson, D.</au><au>Miedzybrodzka, Z.H.</au><au>Jellema, G.</au><au>Logan, G.</au><au>Kennedy, R.D.</au><au>Turkington, R.C.</au><au>McLean, M.H.</au><au>Swinson, D.</au><au>Grabsch, H.I.</au><au>Lord, S.</au><au>Seymour, M.J.</au><au>Hall, P.S.</au><au>Petty, R.D.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>An investigation of the clinical impact and therapeutic relevance of a DNA damage immune response (DDIR) signature in patients with advanced gastroesophageal adenocarcinoma</atitle><jtitle>ESMO open</jtitle><addtitle>ESMO Open</addtitle><date>2024-05-01</date><risdate>2024</risdate><volume>9</volume><issue>5</issue><spage>103450</spage><pages>103450-</pages><artnum>103450</artnum><issn>2059-7029</issn><eissn>2059-7029</eissn><abstract>An improved understanding of which gastroesophageal adenocarcinoma (GOA) patients respond to both chemotherapy and immune checkpoint inhibitors (ICI) is needed. We investigated the predictive role and underlying biology of a 44-gene DNA damage immune response (DDIR) signature in patients with advanced GOA.
Transcriptional profiling was carried out on pretreatment tissue from 252 GOA patients treated with platinum-based chemotherapy (three dose levels) within the randomized phase III GO2 trial. Cross-validation was carried out in two independent GOA cohorts with transcriptional profiling, immune cell immunohistochemistry and epidermal growth factor receptor (EGFR) fluorescent in situ hybridization (FISH) (n = 430).
In the GO2 trial, DDIR-positive tumours had a greater radiological response (51.7% versus 28.5%, P = 0.022) and improved overall survival in a dose-dependent manner (P = 0.028). DDIR positivity was associated with a pretreatment inflamed tumour microenvironment (TME) and increased expression of biomarkers associated with ICI response such as CD274 (programmed death-ligand 1, PD-L1) and a microsatellite instability RNA signature. Consensus pathway analysis identified EGFR as a potential key determinant of the DDIR signature. EGFR amplification was associated with DDIR negativity and an immune cold TME.
Our results indicate the importance of the GOA TME in chemotherapy response, its relationship to DNA damage repair and EGFR as a targetable driver of an immune cold TME. Chemotherapy-sensitive inflamed GOAs could benefit from ICI delivered in combination with standard chemotherapy. Combining EGFR inhibitors and ICIs warrants further investigation in patients with EGFR-amplified tumours.
•The DDIR signature is predictive of chemotherapy response and dose-dependent survival in gastroesophageal adenocarcinoma.•DDIR-positive tumours have an immune hot tumour microenvironment with expression of biomarkers of immunotherapy response.•Epidermal growth factor receptor (EGFR) is identified as a potential driver of an immune cold tumour microenvironment.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>38744099</pmid><doi>10.1016/j.esmoop.2024.103450</doi><orcidid>https://orcid.org/0000-0003-3164-1890</orcidid><orcidid>https://orcid.org/0000-0002-5773-8650</orcidid><orcidid>https://orcid.org/0000-0002-7443-2653</orcidid><orcidid>https://orcid.org/0000-0001-7946-5609</orcidid><orcidid>https://orcid.org/0000-0002-2338-0179</orcidid><orcidid>https://orcid.org/0000-0002-2441-9629</orcidid><orcidid>https://orcid.org/0009-0005-2936-6828</orcidid><orcidid>https://orcid.org/0000-0003-4737-6163</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | ESMO open, 2024-05, Vol.9 (5), p.103450, Article 103450 |
| issn | 2059-7029 2059-7029 |
| language | eng |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | Adenocarcinoma - drug therapy Adenocarcinoma - genetics Adenocarcinoma - immunology Aged Biomarkers, Tumor - metabolism DNA Damage DNA damage immune response epidermal growth factor receptor ErbB Receptors - metabolism Esophageal Neoplasms - drug therapy Esophageal Neoplasms - genetics Esophageal Neoplasms - immunology Female gastroesophageal adenocarcinoma Humans immune checkpoint inhibitors Immune Checkpoint Inhibitors - pharmacology Immune Checkpoint Inhibitors - therapeutic use Male Middle Aged Original Research Stomach Neoplasms - drug therapy Stomach Neoplasms - genetics Stomach Neoplasms - immunology Tumor Microenvironment - immunology tumour microenvironment |
| title | An investigation of the clinical impact and therapeutic relevance of a DNA damage immune response (DDIR) signature in patients with advanced gastroesophageal adenocarcinoma |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-18T13%3A14%3A14IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=An%20investigation%20of%20the%20clinical%20impact%20and%20therapeutic%20relevance%20of%20a%20DNA%20damage%20immune%20response%20(DDIR)%20signature%20in%20patients%20with%20advanced%20gastroesophageal%20adenocarcinoma&rft.jtitle=ESMO%20open&rft.au=Baxter,%20M.A.&rft.date=2024-05-01&rft.volume=9&rft.issue=5&rft.spage=103450&rft.pages=103450-&rft.artnum=103450&rft.issn=2059-7029&rft.eissn=2059-7029&rft_id=info:doi/10.1016/j.esmoop.2024.103450&rft_dat=%3Cproquest_pubme%3E3055451687%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=3055451687&rft_id=info:pmid/38744099&rft_els_id=S2059702924012183&rfr_iscdi=true |