The immune microenvironment after neoadjuvant therapy compared to upfront surgery in patients with pancreatic cancer
Background Patients with resectable and borderline resectable pancreatic ductal adenocarcinoma increasingly receive neoadjuvant therapy prior to surgery. However, the effect of neoadjuvant therapy on the immune microenvironment remains largely unknown. We analyzed the immune microenvironment in panc...
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| Veröffentlicht in: | Journal of cancer research and clinical oncology 2023-11, Vol.149 (16), p.14731-14743 |
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| creator | Zwart, Eline S. van Ee, Thomas Doppenberg, Deesje Farina, Arantza Wilmink, Johanna W. Versteijne, Eva Busch, Olivier R. Besselink, Marc G. Meijer, Laura L. van Kooyk, Yvette Mebius, Reina E. Kazemier, Geert |
| description | Background
Patients with resectable and borderline resectable pancreatic ductal adenocarcinoma increasingly receive neoadjuvant therapy prior to surgery. However, the effect of neoadjuvant therapy on the immune microenvironment remains largely unknown. We analyzed the immune microenvironment in pancreatic cancer tumor tissue samples from patients treated with neoadjuvant therapy compared to patients after upfront surgery to gain knowledge about the immunological environment after therapy.
Methods
Multispectral imaging was performed on tissue from resected specimens from patients with PDAC who underwent upfront surgery (
n
= 10), neoadjuvant FOLFIRINOX (
n
= 10) or gemcitabine + radiotherapy (gem-RT) (
n
= 9) followed by surgery. The samples were selected by a dedicated pancreas pathologist from both the central part and the invasive front of the tumor (by the resected vein or venous surface) and subsequently analyzed using the Vectra Polaris.
Results
Patients receiving neoadjuvant FOLFIRINOX display a more pro-inflammatory immune profile, with less regulatory T cells and more CD8 T cells in the tumor tissue compared to patients receiving neoadjuvant gem-RTgem-RT or undergoing upfront surgery. Furthermore, CD163
+
macrophages were decreased, and a higher CD163
−
macrophages versus CD163
+
macrophages ratio was found in patients with neoadjuvant FOLFIRINOX. In all treatment groups, percentage of FoxP3
+
B cells was significantly higher in tumor tissue compared to adjacent tissue. Furthermore, an increase in regulatory T cells in the tumor tissue was found in patients undergoing upfront surgery or receiving neoadjuvant gem-RT. In the gem-RT group, less CD8 T cells and a higher CD163
+
macrophages to CD8 ratio were noted in the tumor tissue, suggesting a more immune suppressive profile in the tumor tissue.
Conclusion
Patients receiving neoadjuvant FOLFIRINOX display a more pro-inflammatory immune profile compared to patients receiving neoadjuvant gem-RT or undergoing upfront surgery. Furthermore, in all treatment groups, a more immune suppressive microenvironment was found in the tumor tissue compared to the adjacent non-tumorous tissue. |
| doi_str_mv | 10.1007/s00432-023-05219-7 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_10603010</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3153566114</sourcerecordid><originalsourceid>FETCH-LOGICAL-c459t-3dcd3bbe3808c34a9cd67123e0b9d8cf881de3b7b150dcd01ed574a8101b1e333</originalsourceid><addsrcrecordid>eNqFkkuP1DAMxyMEYoeBL8ABReLCpWDXk6Y9IbTiJa3EZTlHaerudDR9kLSzmm-Ph1mWxwFOie2f_3FsK_Uc4TUC2DcJYEN5BjllYHKsMvtArfDkQiLzUK0ALWYSKS7Uk5R2ILax-WN1QdaUlqBaqfl6y7rr-2Vg3XchjjwcujgOPQ-z9u3MUQ88-ma3HLx45i1HPx11GPvJR270POplaiVh1mmJNxyPuhv05OdOBJK-7eatWEOILK6gg1w5PlWPWr9P_OzuXKuvH95fX37Krr58_Hz57ioLG1PNGTWhobpmKqEMtPFVaAqLOTHUVVOGtiyxYaptjQYEBeTG2I0vEbBGJqK1envWnZa65yZISdHv3RS73sejG33n_owM3dbdjAeHUAABgii8ulOI47eF0-z6LgXe7710ZUmO0JApCpSu_w_NS5MXBIZO6Mu_0N24xEFaIVSZI5IR3bXKz5RMJaXI7X3hCO60AO68AE4WwP1YAGcl6cXvX75P-TlxAegMJAkNMrBfb_9D9jsbA76L</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2882113515</pqid></control><display><type>article</type><title>The immune microenvironment after neoadjuvant therapy compared to upfront surgery in patients with pancreatic cancer</title><source>MEDLINE</source><source>SpringerLink Journals</source><creator>Zwart, Eline S. ; van Ee, Thomas ; Doppenberg, Deesje ; Farina, Arantza ; Wilmink, Johanna W. ; Versteijne, Eva ; Busch, Olivier R. ; Besselink, Marc G. ; Meijer, Laura L. ; van Kooyk, Yvette ; Mebius, Reina E. ; Kazemier, Geert</creator><creatorcontrib>Zwart, Eline S. ; van Ee, Thomas ; Doppenberg, Deesje ; Farina, Arantza ; Wilmink, Johanna W. ; Versteijne, Eva ; Busch, Olivier R. ; Besselink, Marc G. ; Meijer, Laura L. ; van Kooyk, Yvette ; Mebius, Reina E. ; Kazemier, Geert</creatorcontrib><description>Background
Patients with resectable and borderline resectable pancreatic ductal adenocarcinoma increasingly receive neoadjuvant therapy prior to surgery. However, the effect of neoadjuvant therapy on the immune microenvironment remains largely unknown. We analyzed the immune microenvironment in pancreatic cancer tumor tissue samples from patients treated with neoadjuvant therapy compared to patients after upfront surgery to gain knowledge about the immunological environment after therapy.
Methods
Multispectral imaging was performed on tissue from resected specimens from patients with PDAC who underwent upfront surgery (
n
= 10), neoadjuvant FOLFIRINOX (
n
= 10) or gemcitabine + radiotherapy (gem-RT) (
n
= 9) followed by surgery. The samples were selected by a dedicated pancreas pathologist from both the central part and the invasive front of the tumor (by the resected vein or venous surface) and subsequently analyzed using the Vectra Polaris.
Results
Patients receiving neoadjuvant FOLFIRINOX display a more pro-inflammatory immune profile, with less regulatory T cells and more CD8 T cells in the tumor tissue compared to patients receiving neoadjuvant gem-RTgem-RT or undergoing upfront surgery. Furthermore, CD163
+
macrophages were decreased, and a higher CD163
−
macrophages versus CD163
+
macrophages ratio was found in patients with neoadjuvant FOLFIRINOX. In all treatment groups, percentage of FoxP3
+
B cells was significantly higher in tumor tissue compared to adjacent tissue. Furthermore, an increase in regulatory T cells in the tumor tissue was found in patients undergoing upfront surgery or receiving neoadjuvant gem-RT. In the gem-RT group, less CD8 T cells and a higher CD163
+
macrophages to CD8 ratio were noted in the tumor tissue, suggesting a more immune suppressive profile in the tumor tissue.
Conclusion
Patients receiving neoadjuvant FOLFIRINOX display a more pro-inflammatory immune profile compared to patients receiving neoadjuvant gem-RT or undergoing upfront surgery. Furthermore, in all treatment groups, a more immune suppressive microenvironment was found in the tumor tissue compared to the adjacent non-tumorous tissue.</description><identifier>ISSN: 0171-5216</identifier><identifier>EISSN: 1432-1335</identifier><identifier>DOI: 10.1007/s00432-023-05219-7</identifier><identifier>PMID: 37587309</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Adenocarcinoma ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Beta cells ; Cancer Research ; Cancer therapies ; Carcinoma, Pancreatic Ductal - drug therapy ; Carcinoma, Pancreatic Ductal - surgery ; CD163 antigen ; CD8 antigen ; Fluorouracil ; Foxp3 protein ; Gemcitabine ; Hematology ; Humans ; Immunoregulation ; Inflammation ; Internal Medicine ; Leucovorin - therapeutic use ; Lymphocytes ; Lymphocytes T ; Macrophages ; Medicine ; Medicine & Public Health ; Microenvironments ; Neoadjuvant Therapy - methods ; Oncology ; pancreas ; Pancreatic cancer ; Pancreatic Neoplasms ; Pancreatic Neoplasms - drug therapy ; Pancreatic Neoplasms - surgery ; Patients ; Radiation therapy ; radiotherapy ; Surgery ; Tumor Microenvironment ; Tumors</subject><ispartof>Journal of cancer research and clinical oncology, 2023-11, Vol.149 (16), p.14731-14743</ispartof><rights>The Author(s) 2023</rights><rights>2023. The Author(s).</rights><rights>The Author(s) 2023. 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><cites>FETCH-LOGICAL-c459t-3dcd3bbe3808c34a9cd67123e0b9d8cf881de3b7b150dcd01ed574a8101b1e333</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00432-023-05219-7$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00432-023-05219-7$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37587309$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zwart, Eline S.</creatorcontrib><creatorcontrib>van Ee, Thomas</creatorcontrib><creatorcontrib>Doppenberg, Deesje</creatorcontrib><creatorcontrib>Farina, Arantza</creatorcontrib><creatorcontrib>Wilmink, Johanna W.</creatorcontrib><creatorcontrib>Versteijne, Eva</creatorcontrib><creatorcontrib>Busch, Olivier R.</creatorcontrib><creatorcontrib>Besselink, Marc G.</creatorcontrib><creatorcontrib>Meijer, Laura L.</creatorcontrib><creatorcontrib>van Kooyk, Yvette</creatorcontrib><creatorcontrib>Mebius, Reina E.</creatorcontrib><creatorcontrib>Kazemier, Geert</creatorcontrib><title>The immune microenvironment after neoadjuvant therapy compared to upfront surgery in patients with pancreatic cancer</title><title>Journal of cancer research and clinical oncology</title><addtitle>J Cancer Res Clin Oncol</addtitle><addtitle>J Cancer Res Clin Oncol</addtitle><description>Background
Patients with resectable and borderline resectable pancreatic ductal adenocarcinoma increasingly receive neoadjuvant therapy prior to surgery. However, the effect of neoadjuvant therapy on the immune microenvironment remains largely unknown. We analyzed the immune microenvironment in pancreatic cancer tumor tissue samples from patients treated with neoadjuvant therapy compared to patients after upfront surgery to gain knowledge about the immunological environment after therapy.
Methods
Multispectral imaging was performed on tissue from resected specimens from patients with PDAC who underwent upfront surgery (
n
= 10), neoadjuvant FOLFIRINOX (
n
= 10) or gemcitabine + radiotherapy (gem-RT) (
n
= 9) followed by surgery. The samples were selected by a dedicated pancreas pathologist from both the central part and the invasive front of the tumor (by the resected vein or venous surface) and subsequently analyzed using the Vectra Polaris.
Results
Patients receiving neoadjuvant FOLFIRINOX display a more pro-inflammatory immune profile, with less regulatory T cells and more CD8 T cells in the tumor tissue compared to patients receiving neoadjuvant gem-RTgem-RT or undergoing upfront surgery. Furthermore, CD163
+
macrophages were decreased, and a higher CD163
−
macrophages versus CD163
+
macrophages ratio was found in patients with neoadjuvant FOLFIRINOX. In all treatment groups, percentage of FoxP3
+
B cells was significantly higher in tumor tissue compared to adjacent tissue. Furthermore, an increase in regulatory T cells in the tumor tissue was found in patients undergoing upfront surgery or receiving neoadjuvant gem-RT. In the gem-RT group, less CD8 T cells and a higher CD163
+
macrophages to CD8 ratio were noted in the tumor tissue, suggesting a more immune suppressive profile in the tumor tissue.
Conclusion
Patients receiving neoadjuvant FOLFIRINOX display a more pro-inflammatory immune profile compared to patients receiving neoadjuvant gem-RT or undergoing upfront surgery. Furthermore, in all treatment groups, a more immune suppressive microenvironment was found in the tumor tissue compared to the adjacent non-tumorous tissue.</description><subject>Adenocarcinoma</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Beta cells</subject><subject>Cancer Research</subject><subject>Cancer therapies</subject><subject>Carcinoma, Pancreatic Ductal - drug therapy</subject><subject>Carcinoma, Pancreatic Ductal - surgery</subject><subject>CD163 antigen</subject><subject>CD8 antigen</subject><subject>Fluorouracil</subject><subject>Foxp3 protein</subject><subject>Gemcitabine</subject><subject>Hematology</subject><subject>Humans</subject><subject>Immunoregulation</subject><subject>Inflammation</subject><subject>Internal Medicine</subject><subject>Leucovorin - therapeutic use</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Macrophages</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Microenvironments</subject><subject>Neoadjuvant Therapy - methods</subject><subject>Oncology</subject><subject>pancreas</subject><subject>Pancreatic cancer</subject><subject>Pancreatic Neoplasms</subject><subject>Pancreatic Neoplasms - drug therapy</subject><subject>Pancreatic Neoplasms - surgery</subject><subject>Patients</subject><subject>Radiation therapy</subject><subject>radiotherapy</subject><subject>Surgery</subject><subject>Tumor Microenvironment</subject><subject>Tumors</subject><issn>0171-5216</issn><issn>1432-1335</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqFkkuP1DAMxyMEYoeBL8ABReLCpWDXk6Y9IbTiJa3EZTlHaerudDR9kLSzmm-Ph1mWxwFOie2f_3FsK_Uc4TUC2DcJYEN5BjllYHKsMvtArfDkQiLzUK0ALWYSKS7Uk5R2ILax-WN1QdaUlqBaqfl6y7rr-2Vg3XchjjwcujgOPQ-z9u3MUQ88-ma3HLx45i1HPx11GPvJR270POplaiVh1mmJNxyPuhv05OdOBJK-7eatWEOILK6gg1w5PlWPWr9P_OzuXKuvH95fX37Krr58_Hz57ioLG1PNGTWhobpmKqEMtPFVaAqLOTHUVVOGtiyxYaptjQYEBeTG2I0vEbBGJqK1envWnZa65yZISdHv3RS73sejG33n_owM3dbdjAeHUAABgii8ulOI47eF0-z6LgXe7710ZUmO0JApCpSu_w_NS5MXBIZO6Mu_0N24xEFaIVSZI5IR3bXKz5RMJaXI7X3hCO60AO68AE4WwP1YAGcl6cXvX75P-TlxAegMJAkNMrBfb_9D9jsbA76L</recordid><startdate>20231101</startdate><enddate>20231101</enddate><creator>Zwart, Eline S.</creator><creator>van Ee, Thomas</creator><creator>Doppenberg, Deesje</creator><creator>Farina, Arantza</creator><creator>Wilmink, Johanna W.</creator><creator>Versteijne, Eva</creator><creator>Busch, Olivier R.</creator><creator>Besselink, Marc G.</creator><creator>Meijer, Laura L.</creator><creator>van Kooyk, Yvette</creator><creator>Mebius, Reina E.</creator><creator>Kazemier, Geert</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</general><scope>C6C</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>3V.</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PHGZM</scope><scope>PHGZT</scope><scope>PJZUB</scope><scope>PKEHL</scope><scope>PPXIY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope><scope>7S9</scope><scope>L.6</scope><scope>5PM</scope></search><sort><creationdate>20231101</creationdate><title>The immune microenvironment after neoadjuvant therapy compared to upfront surgery in patients with pancreatic cancer</title><author>Zwart, Eline S. ; van Ee, Thomas ; Doppenberg, Deesje ; Farina, Arantza ; Wilmink, Johanna W. ; Versteijne, Eva ; Busch, Olivier R. ; Besselink, Marc G. ; Meijer, Laura L. ; van Kooyk, Yvette ; Mebius, Reina E. ; Kazemier, Geert</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c459t-3dcd3bbe3808c34a9cd67123e0b9d8cf881de3b7b150dcd01ed574a8101b1e333</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Adenocarcinoma</topic><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>Beta cells</topic><topic>Cancer Research</topic><topic>Cancer therapies</topic><topic>Carcinoma, Pancreatic Ductal - drug therapy</topic><topic>Carcinoma, Pancreatic Ductal - surgery</topic><topic>CD163 antigen</topic><topic>CD8 antigen</topic><topic>Fluorouracil</topic><topic>Foxp3 protein</topic><topic>Gemcitabine</topic><topic>Hematology</topic><topic>Humans</topic><topic>Immunoregulation</topic><topic>Inflammation</topic><topic>Internal Medicine</topic><topic>Leucovorin - therapeutic use</topic><topic>Lymphocytes</topic><topic>Lymphocytes T</topic><topic>Macrophages</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Microenvironments</topic><topic>Neoadjuvant Therapy - methods</topic><topic>Oncology</topic><topic>pancreas</topic><topic>Pancreatic cancer</topic><topic>Pancreatic Neoplasms</topic><topic>Pancreatic Neoplasms - drug therapy</topic><topic>Pancreatic Neoplasms - surgery</topic><topic>Patients</topic><topic>Radiation therapy</topic><topic>radiotherapy</topic><topic>Surgery</topic><topic>Tumor Microenvironment</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zwart, Eline S.</creatorcontrib><creatorcontrib>van Ee, Thomas</creatorcontrib><creatorcontrib>Doppenberg, Deesje</creatorcontrib><creatorcontrib>Farina, Arantza</creatorcontrib><creatorcontrib>Wilmink, Johanna W.</creatorcontrib><creatorcontrib>Versteijne, Eva</creatorcontrib><creatorcontrib>Busch, Olivier R.</creatorcontrib><creatorcontrib>Besselink, Marc G.</creatorcontrib><creatorcontrib>Meijer, Laura L.</creatorcontrib><creatorcontrib>van Kooyk, Yvette</creatorcontrib><creatorcontrib>Mebius, Reina E.</creatorcontrib><creatorcontrib>Kazemier, Geert</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>Oncogenes and Growth Factors 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>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</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>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Research Library (Corporate)</collection><collection>ProQuest Central (New)</collection><collection>ProQuest One Academic (New)</collection><collection>ProQuest Health & Medical Research Collection</collection><collection>ProQuest One Academic Middle East (New)</collection><collection>ProQuest One Health & Nursing</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 Basic</collection><collection>MEDLINE - Academic</collection><collection>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of cancer research and clinical oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zwart, Eline S.</au><au>van Ee, Thomas</au><au>Doppenberg, Deesje</au><au>Farina, Arantza</au><au>Wilmink, Johanna W.</au><au>Versteijne, Eva</au><au>Busch, Olivier R.</au><au>Besselink, Marc G.</au><au>Meijer, Laura L.</au><au>van Kooyk, Yvette</au><au>Mebius, Reina E.</au><au>Kazemier, Geert</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The immune microenvironment after neoadjuvant therapy compared to upfront surgery in patients with pancreatic cancer</atitle><jtitle>Journal of cancer research and clinical oncology</jtitle><stitle>J Cancer Res Clin Oncol</stitle><addtitle>J Cancer Res Clin Oncol</addtitle><date>2023-11-01</date><risdate>2023</risdate><volume>149</volume><issue>16</issue><spage>14731</spage><epage>14743</epage><pages>14731-14743</pages><issn>0171-5216</issn><eissn>1432-1335</eissn><abstract>Background
Patients with resectable and borderline resectable pancreatic ductal adenocarcinoma increasingly receive neoadjuvant therapy prior to surgery. However, the effect of neoadjuvant therapy on the immune microenvironment remains largely unknown. We analyzed the immune microenvironment in pancreatic cancer tumor tissue samples from patients treated with neoadjuvant therapy compared to patients after upfront surgery to gain knowledge about the immunological environment after therapy.
Methods
Multispectral imaging was performed on tissue from resected specimens from patients with PDAC who underwent upfront surgery (
n
= 10), neoadjuvant FOLFIRINOX (
n
= 10) or gemcitabine + radiotherapy (gem-RT) (
n
= 9) followed by surgery. The samples were selected by a dedicated pancreas pathologist from both the central part and the invasive front of the tumor (by the resected vein or venous surface) and subsequently analyzed using the Vectra Polaris.
Results
Patients receiving neoadjuvant FOLFIRINOX display a more pro-inflammatory immune profile, with less regulatory T cells and more CD8 T cells in the tumor tissue compared to patients receiving neoadjuvant gem-RTgem-RT or undergoing upfront surgery. Furthermore, CD163
+
macrophages were decreased, and a higher CD163
−
macrophages versus CD163
+
macrophages ratio was found in patients with neoadjuvant FOLFIRINOX. In all treatment groups, percentage of FoxP3
+
B cells was significantly higher in tumor tissue compared to adjacent tissue. Furthermore, an increase in regulatory T cells in the tumor tissue was found in patients undergoing upfront surgery or receiving neoadjuvant gem-RT. In the gem-RT group, less CD8 T cells and a higher CD163
+
macrophages to CD8 ratio were noted in the tumor tissue, suggesting a more immune suppressive profile in the tumor tissue.
Conclusion
Patients receiving neoadjuvant FOLFIRINOX display a more pro-inflammatory immune profile compared to patients receiving neoadjuvant gem-RT or undergoing upfront surgery. Furthermore, in all treatment groups, a more immune suppressive microenvironment was found in the tumor tissue compared to the adjacent non-tumorous tissue.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>37587309</pmid><doi>10.1007/s00432-023-05219-7</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Journal of cancer research and clinical oncology, 2023-11, Vol.149 (16), p.14731-14743 |
| issn | 0171-5216 1432-1335 |
| language | eng |
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| source | MEDLINE; SpringerLink Journals |
| subjects | Adenocarcinoma Antineoplastic Combined Chemotherapy Protocols - therapeutic use Beta cells Cancer Research Cancer therapies Carcinoma, Pancreatic Ductal - drug therapy Carcinoma, Pancreatic Ductal - surgery CD163 antigen CD8 antigen Fluorouracil Foxp3 protein Gemcitabine Hematology Humans Immunoregulation Inflammation Internal Medicine Leucovorin - therapeutic use Lymphocytes Lymphocytes T Macrophages Medicine Medicine & Public Health Microenvironments Neoadjuvant Therapy - methods Oncology pancreas Pancreatic cancer Pancreatic Neoplasms Pancreatic Neoplasms - drug therapy Pancreatic Neoplasms - surgery Patients Radiation therapy radiotherapy Surgery Tumor Microenvironment Tumors |
| title | The immune microenvironment after neoadjuvant therapy compared to upfront surgery in patients with pancreatic cancer |
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