Tumor Microenvironment Immune Response in Pancreatic Ductal Adenocarcinoma Patients Treated With Neoadjuvant Therapy
Abstract Background Neoadjuvant folinic acid, fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) and chemoradiation have been used to downstage borderline and locally advanced pancreatic ductal adenocarcinoma (PDAC). Whether neoadjuvant therapy-induced tumor immune response contributes to the im...
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| creator | Michelakos, Theodoros Cai, Lei Villani, Vincenzo Sabbatino, Francesco Kontos, Filippos Fernández-del Castillo, Carlos Yamada, Teppei Neyaz, Azfar Taylor, Martin S Deshpande, Vikram Kurokawa, Tomohiro Ting, David T Qadan, Motaz Weekes, Colin D Allen, Jill N Clark, Jeffrey W Hong, Theodore S Ryan, David P Wo, Jennifer Y Warshaw, Andrew L Lillemoe, Keith D Ferrone, Soldano Ferrone, Cristina R |
| description | Abstract
Background
Neoadjuvant folinic acid, fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) and chemoradiation have been used to downstage borderline and locally advanced pancreatic ductal adenocarcinoma (PDAC). Whether neoadjuvant therapy-induced tumor immune response contributes to the improved survival is unknown. Therefore, we evaluated whether neoadjuvant therapy induces an immune response towards PDAC.
Methods
Clinicopathological variables were collected for surgically resected PDACs at the Massachusetts General Hospital (1998-2016). Neoadjuvant regimens included FOLFIRINOX with or without chemoradiation, proton chemoradiation (25 Gy), photon chemoradiation (50.4 Gy), or no neoadjuvant therapy. Human leukocyte antigen (HLA) class I and II expression and immune cell infiltration (CD4+, FoxP3+, CD8+, granzyme B+ cells, and M2 macrophages) were analyzed immunohistochemically and correlated with clinicopathologic variables. The antitumor immune response was compared among neoadjuvant therapy regimens. All statistical tests were 2-sided.
Results
Two hundred forty-eight PDAC patients were included. The median age was 64 years and 50.0% were female. HLA-A defects were less frequent in the FOLFIRINOX cohort (P = .006). HLA class II expression was lowest in photon and highest in proton patients (P = .02). The FOLFIRINOX cohort exhibited the densest CD8+ cell infiltration (P < .001). FOLFIRINOX and proton patients had the highest CD4+ and lowest T regulatory (FoxP3+) cell density, respectively. M2 macrophage density was statistically significantly higher in the treatment-naïve group (P < .001) in which dense M2 macrophage infiltration was an independent predictor of poor overall survival.
Conclusions
Neoadjuvant FOLFIRINOX with or without chemoradiation may induce immunologically relevant changes in the tumor microenvironment. It may reduce HLA-A defects, increase CD8+ cell density, and decrease T regulatory cell and M2 macrophage density. Therefore, neoadjuvant FOLFIRINOX therapy may benefit from combinations with checkpoint inhibitors, which can enhance patients’ antitumor immune response. |
| doi_str_mv | 10.1093/jnci/djaa073 |
| format | Article |
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Background
Neoadjuvant folinic acid, fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) and chemoradiation have been used to downstage borderline and locally advanced pancreatic ductal adenocarcinoma (PDAC). Whether neoadjuvant therapy-induced tumor immune response contributes to the improved survival is unknown. Therefore, we evaluated whether neoadjuvant therapy induces an immune response towards PDAC.
Methods
Clinicopathological variables were collected for surgically resected PDACs at the Massachusetts General Hospital (1998-2016). Neoadjuvant regimens included FOLFIRINOX with or without chemoradiation, proton chemoradiation (25 Gy), photon chemoradiation (50.4 Gy), or no neoadjuvant therapy. Human leukocyte antigen (HLA) class I and II expression and immune cell infiltration (CD4+, FoxP3+, CD8+, granzyme B+ cells, and M2 macrophages) were analyzed immunohistochemically and correlated with clinicopathologic variables. The antitumor immune response was compared among neoadjuvant therapy regimens. All statistical tests were 2-sided.
Results
Two hundred forty-eight PDAC patients were included. The median age was 64 years and 50.0% were female. HLA-A defects were less frequent in the FOLFIRINOX cohort (P = .006). HLA class II expression was lowest in photon and highest in proton patients (P = .02). The FOLFIRINOX cohort exhibited the densest CD8+ cell infiltration (P < .001). FOLFIRINOX and proton patients had the highest CD4+ and lowest T regulatory (FoxP3+) cell density, respectively. M2 macrophage density was statistically significantly higher in the treatment-naïve group (P < .001) in which dense M2 macrophage infiltration was an independent predictor of poor overall survival.
Conclusions
Neoadjuvant FOLFIRINOX with or without chemoradiation may induce immunologically relevant changes in the tumor microenvironment. It may reduce HLA-A defects, increase CD8+ cell density, and decrease T regulatory cell and M2 macrophage density. Therefore, neoadjuvant FOLFIRINOX therapy may benefit from combinations with checkpoint inhibitors, which can enhance patients’ antitumor immune response.</description><identifier>ISSN: 0027-8874</identifier><identifier>EISSN: 1460-2105</identifier><identifier>DOI: 10.1093/jnci/djaa073</identifier><identifier>PMID: 32497200</identifier><language>eng</language><publisher>United States: Oxford University Press</publisher><subject>5-Fluorouracil ; Adenocarcinoma ; Antigens ; Antitumor activity ; Beta cells ; CD4 antigen ; CD8 antigen ; Cell density ; Chemoradiotherapy ; Defects ; Density ; Folinic acid ; Foxp3 protein ; Granzyme B ; Histocompatibility antigen HLA ; Immune checkpoint ; Immune response ; Immune system ; Infiltration ; Irinotecan ; Leukocytes ; Macrophages ; Metastases ; Oxaliplatin ; Pancreas ; Pancreatic cancer ; Patients ; Photons ; Protons ; Statistical analysis ; Statistical tests ; Survival ; Therapy ; Tumor microenvironment</subject><ispartof>JNCI : Journal of the National Cancer Institute, 2021-02, Vol.113 (2), p.182-191</ispartof><rights>The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com 2020</rights><rights>The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.</rights><rights>The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c444t-8e517fb324a334b9240d4e65726f7061c0a473a59cdac5564d62bb79af3e9d033</citedby><cites>FETCH-LOGICAL-c444t-8e517fb324a334b9240d4e65726f7061c0a473a59cdac5564d62bb79af3e9d033</cites><orcidid>0000-0002-7011-4017 ; 0000-0001-6951-8308 ; 0000-0002-6078-9766 ; 0000-0001-9524-3600 ; 0000-0002-4047-0926 ; 0000-0001-6431-8278</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,1584,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32497200$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Michelakos, Theodoros</creatorcontrib><creatorcontrib>Cai, Lei</creatorcontrib><creatorcontrib>Villani, Vincenzo</creatorcontrib><creatorcontrib>Sabbatino, Francesco</creatorcontrib><creatorcontrib>Kontos, Filippos</creatorcontrib><creatorcontrib>Fernández-del Castillo, Carlos</creatorcontrib><creatorcontrib>Yamada, Teppei</creatorcontrib><creatorcontrib>Neyaz, Azfar</creatorcontrib><creatorcontrib>Taylor, Martin S</creatorcontrib><creatorcontrib>Deshpande, Vikram</creatorcontrib><creatorcontrib>Kurokawa, Tomohiro</creatorcontrib><creatorcontrib>Ting, David T</creatorcontrib><creatorcontrib>Qadan, Motaz</creatorcontrib><creatorcontrib>Weekes, Colin D</creatorcontrib><creatorcontrib>Allen, Jill N</creatorcontrib><creatorcontrib>Clark, Jeffrey W</creatorcontrib><creatorcontrib>Hong, Theodore S</creatorcontrib><creatorcontrib>Ryan, David P</creatorcontrib><creatorcontrib>Wo, Jennifer Y</creatorcontrib><creatorcontrib>Warshaw, Andrew L</creatorcontrib><creatorcontrib>Lillemoe, Keith D</creatorcontrib><creatorcontrib>Ferrone, Soldano</creatorcontrib><creatorcontrib>Ferrone, Cristina R</creatorcontrib><title>Tumor Microenvironment Immune Response in Pancreatic Ductal Adenocarcinoma Patients Treated With Neoadjuvant Therapy</title><title>JNCI : Journal of the National Cancer Institute</title><addtitle>J Natl Cancer Inst</addtitle><description>Abstract
Background
Neoadjuvant folinic acid, fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) and chemoradiation have been used to downstage borderline and locally advanced pancreatic ductal adenocarcinoma (PDAC). Whether neoadjuvant therapy-induced tumor immune response contributes to the improved survival is unknown. Therefore, we evaluated whether neoadjuvant therapy induces an immune response towards PDAC.
Methods
Clinicopathological variables were collected for surgically resected PDACs at the Massachusetts General Hospital (1998-2016). Neoadjuvant regimens included FOLFIRINOX with or without chemoradiation, proton chemoradiation (25 Gy), photon chemoradiation (50.4 Gy), or no neoadjuvant therapy. Human leukocyte antigen (HLA) class I and II expression and immune cell infiltration (CD4+, FoxP3+, CD8+, granzyme B+ cells, and M2 macrophages) were analyzed immunohistochemically and correlated with clinicopathologic variables. The antitumor immune response was compared among neoadjuvant therapy regimens. All statistical tests were 2-sided.
Results
Two hundred forty-eight PDAC patients were included. The median age was 64 years and 50.0% were female. HLA-A defects were less frequent in the FOLFIRINOX cohort (P = .006). HLA class II expression was lowest in photon and highest in proton patients (P = .02). The FOLFIRINOX cohort exhibited the densest CD8+ cell infiltration (P < .001). FOLFIRINOX and proton patients had the highest CD4+ and lowest T regulatory (FoxP3+) cell density, respectively. M2 macrophage density was statistically significantly higher in the treatment-naïve group (P < .001) in which dense M2 macrophage infiltration was an independent predictor of poor overall survival.
Conclusions
Neoadjuvant FOLFIRINOX with or without chemoradiation may induce immunologically relevant changes in the tumor microenvironment. It may reduce HLA-A defects, increase CD8+ cell density, and decrease T regulatory cell and M2 macrophage density. Therefore, neoadjuvant FOLFIRINOX therapy may benefit from combinations with checkpoint inhibitors, which can enhance patients’ antitumor immune response.</description><subject>5-Fluorouracil</subject><subject>Adenocarcinoma</subject><subject>Antigens</subject><subject>Antitumor activity</subject><subject>Beta cells</subject><subject>CD4 antigen</subject><subject>CD8 antigen</subject><subject>Cell density</subject><subject>Chemoradiotherapy</subject><subject>Defects</subject><subject>Density</subject><subject>Folinic acid</subject><subject>Foxp3 protein</subject><subject>Granzyme B</subject><subject>Histocompatibility antigen HLA</subject><subject>Immune checkpoint</subject><subject>Immune response</subject><subject>Immune system</subject><subject>Infiltration</subject><subject>Irinotecan</subject><subject>Leukocytes</subject><subject>Macrophages</subject><subject>Metastases</subject><subject>Oxaliplatin</subject><subject>Pancreas</subject><subject>Pancreatic cancer</subject><subject>Patients</subject><subject>Photons</subject><subject>Protons</subject><subject>Statistical analysis</subject><subject>Statistical tests</subject><subject>Survival</subject><subject>Therapy</subject><subject>Tumor microenvironment</subject><issn>0027-8874</issn><issn>1460-2105</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNp9kU1v1DAURS0EokPLjjWyxIINaV9iO042SFX5qlSgQoNYWi-2wzia2KmdjNR_j0czVGWDN2_h4_uOfAl5VcJ5CS27GLx2F2ZABMmekFXJayiqEsRTsgKoZNE0kp-QFykNkE9b8efkhFW8lRXAiszrZQyRfnU6But3LgY_Wj_T63FcvKU_bJqCT5Y6T2_R62hxdpp-WPSMW3pprA8ao3Y-jJiB2eW3ia73mDX0l5s39JsNaIZlhzl1vbERp_sz8qzHbbIvj_OU_Pz0cX31pbj5_vn66vKm0JzzuWisKGXfZVlkjHdZHQy3tZBV3UuoSw3IJUPRaoNaiJqbuuo62WLPbGuAsVPy_pA7Ld1ojc5yEbdqim7EeK8COvXvjXcb9TvslGwECNbmgDfHgBjuFptmNYQl-uysKlE2teRCQqbeHaj8hylF2z9sKEHtO1L7jtSxo4y_fmz1AP8tJQNvD0BYpv9H_QHc356K</recordid><startdate>20210201</startdate><enddate>20210201</enddate><creator>Michelakos, Theodoros</creator><creator>Cai, Lei</creator><creator>Villani, Vincenzo</creator><creator>Sabbatino, Francesco</creator><creator>Kontos, Filippos</creator><creator>Fernández-del Castillo, Carlos</creator><creator>Yamada, Teppei</creator><creator>Neyaz, Azfar</creator><creator>Taylor, Martin S</creator><creator>Deshpande, Vikram</creator><creator>Kurokawa, Tomohiro</creator><creator>Ting, David T</creator><creator>Qadan, Motaz</creator><creator>Weekes, Colin D</creator><creator>Allen, Jill N</creator><creator>Clark, Jeffrey W</creator><creator>Hong, Theodore S</creator><creator>Ryan, David P</creator><creator>Wo, Jennifer Y</creator><creator>Warshaw, Andrew L</creator><creator>Lillemoe, Keith D</creator><creator>Ferrone, Soldano</creator><creator>Ferrone, Cristina R</creator><general>Oxford University Press</general><general>Oxford Publishing Limited (England)</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TO</scope><scope>7U7</scope><scope>7U9</scope><scope>C1K</scope><scope>H94</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-7011-4017</orcidid><orcidid>https://orcid.org/0000-0001-6951-8308</orcidid><orcidid>https://orcid.org/0000-0002-6078-9766</orcidid><orcidid>https://orcid.org/0000-0001-9524-3600</orcidid><orcidid>https://orcid.org/0000-0002-4047-0926</orcidid><orcidid>https://orcid.org/0000-0001-6431-8278</orcidid></search><sort><creationdate>20210201</creationdate><title>Tumor Microenvironment Immune Response in Pancreatic Ductal Adenocarcinoma Patients Treated With Neoadjuvant Therapy</title><author>Michelakos, Theodoros ; Cai, Lei ; Villani, Vincenzo ; Sabbatino, Francesco ; Kontos, Filippos ; Fernández-del Castillo, Carlos ; Yamada, Teppei ; Neyaz, Azfar ; Taylor, Martin S ; Deshpande, Vikram ; Kurokawa, Tomohiro ; Ting, David T ; Qadan, Motaz ; Weekes, Colin D ; Allen, Jill N ; Clark, Jeffrey W ; Hong, Theodore S ; Ryan, David P ; Wo, Jennifer Y ; Warshaw, Andrew L ; Lillemoe, Keith D ; Ferrone, Soldano ; Ferrone, Cristina R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c444t-8e517fb324a334b9240d4e65726f7061c0a473a59cdac5564d62bb79af3e9d033</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>5-Fluorouracil</topic><topic>Adenocarcinoma</topic><topic>Antigens</topic><topic>Antitumor activity</topic><topic>Beta cells</topic><topic>CD4 antigen</topic><topic>CD8 antigen</topic><topic>Cell density</topic><topic>Chemoradiotherapy</topic><topic>Defects</topic><topic>Density</topic><topic>Folinic acid</topic><topic>Foxp3 protein</topic><topic>Granzyme B</topic><topic>Histocompatibility antigen HLA</topic><topic>Immune checkpoint</topic><topic>Immune response</topic><topic>Immune system</topic><topic>Infiltration</topic><topic>Irinotecan</topic><topic>Leukocytes</topic><topic>Macrophages</topic><topic>Metastases</topic><topic>Oxaliplatin</topic><topic>Pancreas</topic><topic>Pancreatic cancer</topic><topic>Patients</topic><topic>Photons</topic><topic>Protons</topic><topic>Statistical analysis</topic><topic>Statistical tests</topic><topic>Survival</topic><topic>Therapy</topic><topic>Tumor microenvironment</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Michelakos, Theodoros</creatorcontrib><creatorcontrib>Cai, Lei</creatorcontrib><creatorcontrib>Villani, Vincenzo</creatorcontrib><creatorcontrib>Sabbatino, Francesco</creatorcontrib><creatorcontrib>Kontos, Filippos</creatorcontrib><creatorcontrib>Fernández-del Castillo, Carlos</creatorcontrib><creatorcontrib>Yamada, Teppei</creatorcontrib><creatorcontrib>Neyaz, Azfar</creatorcontrib><creatorcontrib>Taylor, Martin S</creatorcontrib><creatorcontrib>Deshpande, Vikram</creatorcontrib><creatorcontrib>Kurokawa, Tomohiro</creatorcontrib><creatorcontrib>Ting, David T</creatorcontrib><creatorcontrib>Qadan, Motaz</creatorcontrib><creatorcontrib>Weekes, Colin D</creatorcontrib><creatorcontrib>Allen, Jill N</creatorcontrib><creatorcontrib>Clark, Jeffrey W</creatorcontrib><creatorcontrib>Hong, Theodore S</creatorcontrib><creatorcontrib>Ryan, David P</creatorcontrib><creatorcontrib>Wo, Jennifer Y</creatorcontrib><creatorcontrib>Warshaw, Andrew L</creatorcontrib><creatorcontrib>Lillemoe, Keith D</creatorcontrib><creatorcontrib>Ferrone, Soldano</creatorcontrib><creatorcontrib>Ferrone, Cristina R</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>JNCI : Journal of the National Cancer Institute</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Michelakos, Theodoros</au><au>Cai, Lei</au><au>Villani, Vincenzo</au><au>Sabbatino, Francesco</au><au>Kontos, Filippos</au><au>Fernández-del Castillo, Carlos</au><au>Yamada, Teppei</au><au>Neyaz, Azfar</au><au>Taylor, Martin S</au><au>Deshpande, Vikram</au><au>Kurokawa, Tomohiro</au><au>Ting, David T</au><au>Qadan, Motaz</au><au>Weekes, Colin D</au><au>Allen, Jill N</au><au>Clark, Jeffrey W</au><au>Hong, Theodore S</au><au>Ryan, David P</au><au>Wo, Jennifer Y</au><au>Warshaw, Andrew L</au><au>Lillemoe, Keith D</au><au>Ferrone, Soldano</au><au>Ferrone, Cristina R</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Tumor Microenvironment Immune Response in Pancreatic Ductal Adenocarcinoma Patients Treated With Neoadjuvant Therapy</atitle><jtitle>JNCI : Journal of the National Cancer Institute</jtitle><addtitle>J Natl Cancer Inst</addtitle><date>2021-02-01</date><risdate>2021</risdate><volume>113</volume><issue>2</issue><spage>182</spage><epage>191</epage><pages>182-191</pages><issn>0027-8874</issn><eissn>1460-2105</eissn><abstract>Abstract
Background
Neoadjuvant folinic acid, fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) and chemoradiation have been used to downstage borderline and locally advanced pancreatic ductal adenocarcinoma (PDAC). Whether neoadjuvant therapy-induced tumor immune response contributes to the improved survival is unknown. Therefore, we evaluated whether neoadjuvant therapy induces an immune response towards PDAC.
Methods
Clinicopathological variables were collected for surgically resected PDACs at the Massachusetts General Hospital (1998-2016). Neoadjuvant regimens included FOLFIRINOX with or without chemoradiation, proton chemoradiation (25 Gy), photon chemoradiation (50.4 Gy), or no neoadjuvant therapy. Human leukocyte antigen (HLA) class I and II expression and immune cell infiltration (CD4+, FoxP3+, CD8+, granzyme B+ cells, and M2 macrophages) were analyzed immunohistochemically and correlated with clinicopathologic variables. The antitumor immune response was compared among neoadjuvant therapy regimens. All statistical tests were 2-sided.
Results
Two hundred forty-eight PDAC patients were included. The median age was 64 years and 50.0% were female. HLA-A defects were less frequent in the FOLFIRINOX cohort (P = .006). HLA class II expression was lowest in photon and highest in proton patients (P = .02). The FOLFIRINOX cohort exhibited the densest CD8+ cell infiltration (P < .001). FOLFIRINOX and proton patients had the highest CD4+ and lowest T regulatory (FoxP3+) cell density, respectively. M2 macrophage density was statistically significantly higher in the treatment-naïve group (P < .001) in which dense M2 macrophage infiltration was an independent predictor of poor overall survival.
Conclusions
Neoadjuvant FOLFIRINOX with or without chemoradiation may induce immunologically relevant changes in the tumor microenvironment. It may reduce HLA-A defects, increase CD8+ cell density, and decrease T regulatory cell and M2 macrophage density. Therefore, neoadjuvant FOLFIRINOX therapy may benefit from combinations with checkpoint inhibitors, which can enhance patients’ antitumor immune response.</abstract><cop>United States</cop><pub>Oxford University Press</pub><pmid>32497200</pmid><doi>10.1093/jnci/djaa073</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-7011-4017</orcidid><orcidid>https://orcid.org/0000-0001-6951-8308</orcidid><orcidid>https://orcid.org/0000-0002-6078-9766</orcidid><orcidid>https://orcid.org/0000-0001-9524-3600</orcidid><orcidid>https://orcid.org/0000-0002-4047-0926</orcidid><orcidid>https://orcid.org/0000-0001-6431-8278</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0027-8874 |
| ispartof | JNCI : Journal of the National Cancer Institute, 2021-02, Vol.113 (2), p.182-191 |
| issn | 0027-8874 1460-2105 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7850539 |
| source | Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Oxford University Press Journals All Titles (1996-Current); Alma/SFX Local Collection |
| subjects | 5-Fluorouracil Adenocarcinoma Antigens Antitumor activity Beta cells CD4 antigen CD8 antigen Cell density Chemoradiotherapy Defects Density Folinic acid Foxp3 protein Granzyme B Histocompatibility antigen HLA Immune checkpoint Immune response Immune system Infiltration Irinotecan Leukocytes Macrophages Metastases Oxaliplatin Pancreas Pancreatic cancer Patients Photons Protons Statistical analysis Statistical tests Survival Therapy Tumor microenvironment |
| title | Tumor Microenvironment Immune Response in Pancreatic Ductal Adenocarcinoma Patients Treated With Neoadjuvant Therapy |
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