STAT3 Modulation of Regulatory T Cells in Response to Radiation Therapy in Head and Neck Cancer
Abstract Background Radioresistance represents a major problem in the treatment of head and neck cancer (HNC) patients. To improve response, understanding tumor microenvironmental factors that contribute to radiation resistance is important. Regulatory T cells (Tregs) are enriched in numerous cancer...
Gespeichert in:
| Veröffentlicht in: | JNCI : Journal of the National Cancer Institute 2019-12, Vol.111 (12), p.1339-1349 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1349 |
|---|---|
| container_issue | 12 |
| container_start_page | 1339 |
| container_title | JNCI : Journal of the National Cancer Institute |
| container_volume | 111 |
| creator | Oweida, Ayman J Darragh, Laurel Phan, Andy Binder, David Bhatia, Shilpa Mueller, Adam Court, Benjamin Van Milner, Dallin Raben, David Woessner, Richard Heasley, Lynn Nemenoff, Raphael Clambey, Eric Karam, Sana D |
| description | Abstract
Background
Radioresistance represents a major problem in the treatment of head and neck cancer (HNC) patients. To improve response, understanding tumor microenvironmental factors that contribute to radiation resistance is important. Regulatory T cells (Tregs) are enriched in numerous cancers and can dampen the response to radiation by creating an immune-inhibitory microenvironment. The purpose of this study was to investigate mechanisms of Treg modulation by radiation in HNC.
Methods
We utilized an orthotopic mouse model of HNC. Anti-CD25 was used for Treg depletion. Image-guided radiation was delivered to a dose of 10 Gy. Flow cytometry was used to analyze abundance and function of intratumoral immune cells. Enzyme-linked immunosorbent assay was performed to assess secreted factors. For immune-modulating therapies, anti–PD-L1, anti-CTLA-4, and STAT3 antisense oligonucleotide (ASO) were used. All statistical tests were two-sided.
Results
Treatment with anti-CD25 and radiation led to tumor eradication (57.1%, n = 4 of 7 mice), enhanced T-cell cytotoxicity compared with RT alone (CD4 effector T cells [Teff]: RT group mean = 5.37 [ 0.58] vs RT + αCD25 group mean =10.71 [0.67], P = .005; CD8 Teff: RT group mean = 9.98 [0.81] vs RT + αCD25 group mean =16.88 [2.49], P = .01) and induced tumor antigen-specific memory response (100.0%, n = 4 mice). In contrast, radiation alone or when combined with anti-CTLA4 did not lead to durable tumor control (0.0%, n = 7 mice). STAT3 inhibition in combination with radiation, but not as a single agent, improved tumor growth delay, decreased Tregs, myeloid-derived suppressor cells, and M2 macrophages and enhanced effector T cells and M1 macrophages. Experiments in nude mice inhibited the benefit of STAT3 ASO and radiation.
Conclusion
We propose that STAT3 inhibition is a viable and potent therapeutic target against Tregs. Our data support the design of clinical trials integrating STAT3 ASO in the standard of care for cancer patients receiving radiation. |
| doi_str_mv | 10.1093/jnci/djz036 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6910208</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><oup_id>10.1093/jnci/djz036</oup_id><sourcerecordid>2502816859</sourcerecordid><originalsourceid>FETCH-LOGICAL-c482t-4ae0f17fe58ea2b789c43442f99c935b01adb938281e3e18d066a61c979796043</originalsourceid><addsrcrecordid>eNp9kc2LFDEQxYMo7rh68i4BwYu0W_nodHIRlkFdYVVY23PIpKt3e-xN2qRbGP96M_S66MXKoajkx3tFHiHPGbxhYMTZPvjhrNv_AqEekA2TCirOoH5INgC8qbRu5Al5kvMeShkuH5MTAVoJLcWG2K_teSvop9gto5uHGGjs6RVeH6eYDrSlWxzHTIdQbvMUQ0Y6R3rlumHF2xtMbjocgQt0HXWho5_Rf6dbFzymp-RR78aMz-76Kfn2_l27vaguv3z4uD2_rLzUfK6kQ-hZ02Ot0fFdo42XQkreG-ONqHfAXLczQnPNUCDTHSjlFPOmKUeBFKfk7ao7Lbtb7DyGObnRTmm4delgoxvsvy9huLHX8adVhgEHXQRe3gmk-GPBPNt9XFIoO1teQ_FVujaFer1SPsWcE_b3DgzsMQ17TMOuaRT6xd9L3bN_vr8Ar1YgLtN_lX4DxbeTEQ</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2502816859</pqid></control><display><type>article</type><title>STAT3 Modulation of Regulatory T Cells in Response to Radiation Therapy in Head and Neck Cancer</title><source>Oxford University Press Journals All Titles (1996-Current)</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Alma/SFX Local Collection</source><creator>Oweida, Ayman J ; Darragh, Laurel ; Phan, Andy ; Binder, David ; Bhatia, Shilpa ; Mueller, Adam ; Court, Benjamin Van ; Milner, Dallin ; Raben, David ; Woessner, Richard ; Heasley, Lynn ; Nemenoff, Raphael ; Clambey, Eric ; Karam, Sana D</creator><creatorcontrib>Oweida, Ayman J ; Darragh, Laurel ; Phan, Andy ; Binder, David ; Bhatia, Shilpa ; Mueller, Adam ; Court, Benjamin Van ; Milner, Dallin ; Raben, David ; Woessner, Richard ; Heasley, Lynn ; Nemenoff, Raphael ; Clambey, Eric ; Karam, Sana D</creatorcontrib><description>Abstract
Background
Radioresistance represents a major problem in the treatment of head and neck cancer (HNC) patients. To improve response, understanding tumor microenvironmental factors that contribute to radiation resistance is important. Regulatory T cells (Tregs) are enriched in numerous cancers and can dampen the response to radiation by creating an immune-inhibitory microenvironment. The purpose of this study was to investigate mechanisms of Treg modulation by radiation in HNC.
Methods
We utilized an orthotopic mouse model of HNC. Anti-CD25 was used for Treg depletion. Image-guided radiation was delivered to a dose of 10 Gy. Flow cytometry was used to analyze abundance and function of intratumoral immune cells. Enzyme-linked immunosorbent assay was performed to assess secreted factors. For immune-modulating therapies, anti–PD-L1, anti-CTLA-4, and STAT3 antisense oligonucleotide (ASO) were used. All statistical tests were two-sided.
Results
Treatment with anti-CD25 and radiation led to tumor eradication (57.1%, n = 4 of 7 mice), enhanced T-cell cytotoxicity compared with RT alone (CD4 effector T cells [Teff]: RT group mean = 5.37 [ 0.58] vs RT + αCD25 group mean =10.71 [0.67], P = .005; CD8 Teff: RT group mean = 9.98 [0.81] vs RT + αCD25 group mean =16.88 [2.49], P = .01) and induced tumor antigen-specific memory response (100.0%, n = 4 mice). In contrast, radiation alone or when combined with anti-CTLA4 did not lead to durable tumor control (0.0%, n = 7 mice). STAT3 inhibition in combination with radiation, but not as a single agent, improved tumor growth delay, decreased Tregs, myeloid-derived suppressor cells, and M2 macrophages and enhanced effector T cells and M1 macrophages. Experiments in nude mice inhibited the benefit of STAT3 ASO and radiation.
Conclusion
We propose that STAT3 inhibition is a viable and potent therapeutic target against Tregs. Our data support the design of clinical trials integrating STAT3 ASO in the standard of care for cancer patients receiving radiation.</description><identifier>ISSN: 0027-8874</identifier><identifier>EISSN: 1460-2105</identifier><identifier>DOI: 10.1093/jnci/djz036</identifier><identifier>PMID: 30863843</identifier><language>eng</language><publisher>United States: Oxford University Press</publisher><subject>Antigens ; Antisense oligonucleotides ; Cancer ; Cancer therapies ; CD25 antigen ; CD4 antigen ; CD8 antigen ; Clinical trials ; CTLA-4 protein ; Cytotoxicity ; Depletion ; Effector cells ; Enzyme-linked immunosorbent assay ; Flow cytometry ; Head & neck cancer ; Immune system ; Immunological memory ; Immunomodulation ; Immunoregulation ; Lymphocytes ; Lymphocytes T ; Macrophages ; Microenvironments ; Modulation ; Patients ; PD-L1 protein ; Radiation ; Radiation therapy ; Radiation tolerance ; Radioresistance ; Stat3 protein ; Statistical analysis ; Statistical tests ; Suppressor cells ; Toxicity ; Tumors</subject><ispartof>JNCI : Journal of the National Cancer Institute, 2019-12, Vol.111 (12), p.1339-1349</ispartof><rights>The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com. 2019</rights><rights>The Author(s) 2019. 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-c482t-4ae0f17fe58ea2b789c43442f99c935b01adb938281e3e18d066a61c979796043</citedby><cites>FETCH-LOGICAL-c482t-4ae0f17fe58ea2b789c43442f99c935b01adb938281e3e18d066a61c979796043</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,1578,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30863843$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Oweida, Ayman J</creatorcontrib><creatorcontrib>Darragh, Laurel</creatorcontrib><creatorcontrib>Phan, Andy</creatorcontrib><creatorcontrib>Binder, David</creatorcontrib><creatorcontrib>Bhatia, Shilpa</creatorcontrib><creatorcontrib>Mueller, Adam</creatorcontrib><creatorcontrib>Court, Benjamin Van</creatorcontrib><creatorcontrib>Milner, Dallin</creatorcontrib><creatorcontrib>Raben, David</creatorcontrib><creatorcontrib>Woessner, Richard</creatorcontrib><creatorcontrib>Heasley, Lynn</creatorcontrib><creatorcontrib>Nemenoff, Raphael</creatorcontrib><creatorcontrib>Clambey, Eric</creatorcontrib><creatorcontrib>Karam, Sana D</creatorcontrib><title>STAT3 Modulation of Regulatory T Cells in Response to Radiation Therapy in Head and Neck Cancer</title><title>JNCI : Journal of the National Cancer Institute</title><addtitle>J Natl Cancer Inst</addtitle><description>Abstract
Background
Radioresistance represents a major problem in the treatment of head and neck cancer (HNC) patients. To improve response, understanding tumor microenvironmental factors that contribute to radiation resistance is important. Regulatory T cells (Tregs) are enriched in numerous cancers and can dampen the response to radiation by creating an immune-inhibitory microenvironment. The purpose of this study was to investigate mechanisms of Treg modulation by radiation in HNC.
Methods
We utilized an orthotopic mouse model of HNC. Anti-CD25 was used for Treg depletion. Image-guided radiation was delivered to a dose of 10 Gy. Flow cytometry was used to analyze abundance and function of intratumoral immune cells. Enzyme-linked immunosorbent assay was performed to assess secreted factors. For immune-modulating therapies, anti–PD-L1, anti-CTLA-4, and STAT3 antisense oligonucleotide (ASO) were used. All statistical tests were two-sided.
Results
Treatment with anti-CD25 and radiation led to tumor eradication (57.1%, n = 4 of 7 mice), enhanced T-cell cytotoxicity compared with RT alone (CD4 effector T cells [Teff]: RT group mean = 5.37 [ 0.58] vs RT + αCD25 group mean =10.71 [0.67], P = .005; CD8 Teff: RT group mean = 9.98 [0.81] vs RT + αCD25 group mean =16.88 [2.49], P = .01) and induced tumor antigen-specific memory response (100.0%, n = 4 mice). In contrast, radiation alone or when combined with anti-CTLA4 did not lead to durable tumor control (0.0%, n = 7 mice). STAT3 inhibition in combination with radiation, but not as a single agent, improved tumor growth delay, decreased Tregs, myeloid-derived suppressor cells, and M2 macrophages and enhanced effector T cells and M1 macrophages. Experiments in nude mice inhibited the benefit of STAT3 ASO and radiation.
Conclusion
We propose that STAT3 inhibition is a viable and potent therapeutic target against Tregs. Our data support the design of clinical trials integrating STAT3 ASO in the standard of care for cancer patients receiving radiation.</description><subject>Antigens</subject><subject>Antisense oligonucleotides</subject><subject>Cancer</subject><subject>Cancer therapies</subject><subject>CD25 antigen</subject><subject>CD4 antigen</subject><subject>CD8 antigen</subject><subject>Clinical trials</subject><subject>CTLA-4 protein</subject><subject>Cytotoxicity</subject><subject>Depletion</subject><subject>Effector cells</subject><subject>Enzyme-linked immunosorbent assay</subject><subject>Flow cytometry</subject><subject>Head & neck cancer</subject><subject>Immune system</subject><subject>Immunological memory</subject><subject>Immunomodulation</subject><subject>Immunoregulation</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Macrophages</subject><subject>Microenvironments</subject><subject>Modulation</subject><subject>Patients</subject><subject>PD-L1 protein</subject><subject>Radiation</subject><subject>Radiation therapy</subject><subject>Radiation tolerance</subject><subject>Radioresistance</subject><subject>Stat3 protein</subject><subject>Statistical analysis</subject><subject>Statistical tests</subject><subject>Suppressor cells</subject><subject>Toxicity</subject><subject>Tumors</subject><issn>0027-8874</issn><issn>1460-2105</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNp9kc2LFDEQxYMo7rh68i4BwYu0W_nodHIRlkFdYVVY23PIpKt3e-xN2qRbGP96M_S66MXKoajkx3tFHiHPGbxhYMTZPvjhrNv_AqEekA2TCirOoH5INgC8qbRu5Al5kvMeShkuH5MTAVoJLcWG2K_teSvop9gto5uHGGjs6RVeH6eYDrSlWxzHTIdQbvMUQ0Y6R3rlumHF2xtMbjocgQt0HXWho5_Rf6dbFzymp-RR78aMz-76Kfn2_l27vaguv3z4uD2_rLzUfK6kQ-hZ02Ot0fFdo42XQkreG-ONqHfAXLczQnPNUCDTHSjlFPOmKUeBFKfk7ao7Lbtb7DyGObnRTmm4delgoxvsvy9huLHX8adVhgEHXQRe3gmk-GPBPNt9XFIoO1teQ_FVujaFer1SPsWcE_b3DgzsMQ17TMOuaRT6xd9L3bN_vr8Ar1YgLtN_lX4DxbeTEQ</recordid><startdate>20191201</startdate><enddate>20191201</enddate><creator>Oweida, Ayman J</creator><creator>Darragh, Laurel</creator><creator>Phan, Andy</creator><creator>Binder, David</creator><creator>Bhatia, Shilpa</creator><creator>Mueller, Adam</creator><creator>Court, Benjamin Van</creator><creator>Milner, Dallin</creator><creator>Raben, David</creator><creator>Woessner, Richard</creator><creator>Heasley, Lynn</creator><creator>Nemenoff, Raphael</creator><creator>Clambey, Eric</creator><creator>Karam, Sana D</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></search><sort><creationdate>20191201</creationdate><title>STAT3 Modulation of Regulatory T Cells in Response to Radiation Therapy in Head and Neck Cancer</title><author>Oweida, Ayman J ; Darragh, Laurel ; Phan, Andy ; Binder, David ; Bhatia, Shilpa ; Mueller, Adam ; Court, Benjamin Van ; Milner, Dallin ; Raben, David ; Woessner, Richard ; Heasley, Lynn ; Nemenoff, Raphael ; Clambey, Eric ; Karam, Sana D</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c482t-4ae0f17fe58ea2b789c43442f99c935b01adb938281e3e18d066a61c979796043</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Antigens</topic><topic>Antisense oligonucleotides</topic><topic>Cancer</topic><topic>Cancer therapies</topic><topic>CD25 antigen</topic><topic>CD4 antigen</topic><topic>CD8 antigen</topic><topic>Clinical trials</topic><topic>CTLA-4 protein</topic><topic>Cytotoxicity</topic><topic>Depletion</topic><topic>Effector cells</topic><topic>Enzyme-linked immunosorbent assay</topic><topic>Flow cytometry</topic><topic>Head & neck cancer</topic><topic>Immune system</topic><topic>Immunological memory</topic><topic>Immunomodulation</topic><topic>Immunoregulation</topic><topic>Lymphocytes</topic><topic>Lymphocytes T</topic><topic>Macrophages</topic><topic>Microenvironments</topic><topic>Modulation</topic><topic>Patients</topic><topic>PD-L1 protein</topic><topic>Radiation</topic><topic>Radiation therapy</topic><topic>Radiation tolerance</topic><topic>Radioresistance</topic><topic>Stat3 protein</topic><topic>Statistical analysis</topic><topic>Statistical tests</topic><topic>Suppressor cells</topic><topic>Toxicity</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Oweida, Ayman J</creatorcontrib><creatorcontrib>Darragh, Laurel</creatorcontrib><creatorcontrib>Phan, Andy</creatorcontrib><creatorcontrib>Binder, David</creatorcontrib><creatorcontrib>Bhatia, Shilpa</creatorcontrib><creatorcontrib>Mueller, Adam</creatorcontrib><creatorcontrib>Court, Benjamin Van</creatorcontrib><creatorcontrib>Milner, Dallin</creatorcontrib><creatorcontrib>Raben, David</creatorcontrib><creatorcontrib>Woessner, Richard</creatorcontrib><creatorcontrib>Heasley, Lynn</creatorcontrib><creatorcontrib>Nemenoff, Raphael</creatorcontrib><creatorcontrib>Clambey, Eric</creatorcontrib><creatorcontrib>Karam, Sana D</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>Oweida, Ayman J</au><au>Darragh, Laurel</au><au>Phan, Andy</au><au>Binder, David</au><au>Bhatia, Shilpa</au><au>Mueller, Adam</au><au>Court, Benjamin Van</au><au>Milner, Dallin</au><au>Raben, David</au><au>Woessner, Richard</au><au>Heasley, Lynn</au><au>Nemenoff, Raphael</au><au>Clambey, Eric</au><au>Karam, Sana D</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>STAT3 Modulation of Regulatory T Cells in Response to Radiation Therapy in Head and Neck Cancer</atitle><jtitle>JNCI : Journal of the National Cancer Institute</jtitle><addtitle>J Natl Cancer Inst</addtitle><date>2019-12-01</date><risdate>2019</risdate><volume>111</volume><issue>12</issue><spage>1339</spage><epage>1349</epage><pages>1339-1349</pages><issn>0027-8874</issn><eissn>1460-2105</eissn><abstract>Abstract
Background
Radioresistance represents a major problem in the treatment of head and neck cancer (HNC) patients. To improve response, understanding tumor microenvironmental factors that contribute to radiation resistance is important. Regulatory T cells (Tregs) are enriched in numerous cancers and can dampen the response to radiation by creating an immune-inhibitory microenvironment. The purpose of this study was to investigate mechanisms of Treg modulation by radiation in HNC.
Methods
We utilized an orthotopic mouse model of HNC. Anti-CD25 was used for Treg depletion. Image-guided radiation was delivered to a dose of 10 Gy. Flow cytometry was used to analyze abundance and function of intratumoral immune cells. Enzyme-linked immunosorbent assay was performed to assess secreted factors. For immune-modulating therapies, anti–PD-L1, anti-CTLA-4, and STAT3 antisense oligonucleotide (ASO) were used. All statistical tests were two-sided.
Results
Treatment with anti-CD25 and radiation led to tumor eradication (57.1%, n = 4 of 7 mice), enhanced T-cell cytotoxicity compared with RT alone (CD4 effector T cells [Teff]: RT group mean = 5.37 [ 0.58] vs RT + αCD25 group mean =10.71 [0.67], P = .005; CD8 Teff: RT group mean = 9.98 [0.81] vs RT + αCD25 group mean =16.88 [2.49], P = .01) and induced tumor antigen-specific memory response (100.0%, n = 4 mice). In contrast, radiation alone or when combined with anti-CTLA4 did not lead to durable tumor control (0.0%, n = 7 mice). STAT3 inhibition in combination with radiation, but not as a single agent, improved tumor growth delay, decreased Tregs, myeloid-derived suppressor cells, and M2 macrophages and enhanced effector T cells and M1 macrophages. Experiments in nude mice inhibited the benefit of STAT3 ASO and radiation.
Conclusion
We propose that STAT3 inhibition is a viable and potent therapeutic target against Tregs. Our data support the design of clinical trials integrating STAT3 ASO in the standard of care for cancer patients receiving radiation.</abstract><cop>United States</cop><pub>Oxford University Press</pub><pmid>30863843</pmid><doi>10.1093/jnci/djz036</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0027-8874 |
| ispartof | JNCI : Journal of the National Cancer Institute, 2019-12, Vol.111 (12), p.1339-1349 |
| issn | 0027-8874 1460-2105 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6910208 |
| source | Oxford University Press Journals All Titles (1996-Current); Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Antigens Antisense oligonucleotides Cancer Cancer therapies CD25 antigen CD4 antigen CD8 antigen Clinical trials CTLA-4 protein Cytotoxicity Depletion Effector cells Enzyme-linked immunosorbent assay Flow cytometry Head & neck cancer Immune system Immunological memory Immunomodulation Immunoregulation Lymphocytes Lymphocytes T Macrophages Microenvironments Modulation Patients PD-L1 protein Radiation Radiation therapy Radiation tolerance Radioresistance Stat3 protein Statistical analysis Statistical tests Suppressor cells Toxicity Tumors |
| title | STAT3 Modulation of Regulatory T Cells in Response to Radiation Therapy in Head and Neck Cancer |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-30T20%3A35%3A15IST&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=STAT3%20Modulation%20of%20Regulatory%20T%20Cells%20in%20Response%20to%20Radiation%20Therapy%20in%20Head%20and%20Neck%20Cancer&rft.jtitle=JNCI%20:%20Journal%20of%20the%20National%20Cancer%20Institute&rft.au=Oweida,%20Ayman%20J&rft.date=2019-12-01&rft.volume=111&rft.issue=12&rft.spage=1339&rft.epage=1349&rft.pages=1339-1349&rft.issn=0027-8874&rft.eissn=1460-2105&rft_id=info:doi/10.1093/jnci/djz036&rft_dat=%3Cproquest_pubme%3E2502816859%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=2502816859&rft_id=info:pmid/30863843&rft_oup_id=10.1093/jnci/djz036&rfr_iscdi=true |