Tumor immune microenvironment in cancer patients with leukocytosis
Tumor-related leukocytosis (TRL) is correlated with poor survival in various types of cancers, but the microenvironment of TRL-associated human tumors has not been fully elucidated. Here, we aimed to characterize the immune microenvironment of cancer patients with TRL. The transcriptional signatures...
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| Veröffentlicht in: | Cancer Immunology, Immunotherapy Immunotherapy, 2020-07, Vol.69 (7), p.1265-1277 |
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| creator | Kim, Kyung Hwan Sim, Nam Suk Chang, Jee Suk Kim, Yong Bae |
| description | Tumor-related leukocytosis (TRL) is correlated with poor survival in various types of cancers, but the microenvironment of TRL-associated human tumors has not been fully elucidated. Here, we aimed to characterize the immune microenvironment of cancer patients with TRL. The transcriptional signatures of tumor tissues obtained from cervical cancer patients with (TRL
pos
) and without TRL (TRL
neg
) were compared. As a surrogate for TRL diagnosis, a leukocytosis signature (LS) score was derived using genes differentially expressed between TRL
pos
and TRL
neg
tumors. The immunological profiles of patients in the TCGA database with high (LS
high
) or low LS scores were compared. TRL
pos
tumors were transcriptionally distinct from TRL
neg
tumors, exhibiting up-regulation of radioresistance and down-regulation of adaptive immune response-related genes. In the TCGA cervical cancer cohort (
n
= 303), patients with high LS had inferior survival rates compared to those with low LS (
P
= 0.023). LS
high
tumors were enriched in radioresistance, wound healing, and myeloid-derived suppressor cell (MDSC) signatures and had a higher infiltration of M2 macrophages and a lower infiltration of M1 macrophages and lymphocytes. LS
high
tumors also expressed higher levels of CXCR2 chemokines,
CSF2
, and
CSF3
. In the pan-cancer cohort (
n
= 9984), LS
high
tumors also exhibited poor survival, signatures of a suppressive immune microenvironment, and higher expression of CXCR2 chemokines. Our data provide evidence for a suppressive immune microenvironment in patients with TRL and suggest promising targets, such as the CXCR2 axis, for its therapeutic intervention. |
| doi_str_mv | 10.1007/s00262-020-02545-4 |
| format | Article |
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pos
) and without TRL (TRL
neg
) were compared. As a surrogate for TRL diagnosis, a leukocytosis signature (LS) score was derived using genes differentially expressed between TRL
pos
and TRL
neg
tumors. The immunological profiles of patients in the TCGA database with high (LS
high
) or low LS scores were compared. TRL
pos
tumors were transcriptionally distinct from TRL
neg
tumors, exhibiting up-regulation of radioresistance and down-regulation of adaptive immune response-related genes. In the TCGA cervical cancer cohort (
n
= 303), patients with high LS had inferior survival rates compared to those with low LS (
P
= 0.023). LS
high
tumors were enriched in radioresistance, wound healing, and myeloid-derived suppressor cell (MDSC) signatures and had a higher infiltration of M2 macrophages and a lower infiltration of M1 macrophages and lymphocytes. LS
high
tumors also expressed higher levels of CXCR2 chemokines,
CSF2
, and
CSF3
. In the pan-cancer cohort (
n
= 9984), LS
high
tumors also exhibited poor survival, signatures of a suppressive immune microenvironment, and higher expression of CXCR2 chemokines. Our data provide evidence for a suppressive immune microenvironment in patients with TRL and suggest promising targets, such as the CXCR2 axis, for its therapeutic intervention.</description><identifier>ISSN: 0340-7004</identifier><identifier>EISSN: 1432-0851</identifier><identifier>DOI: 10.1007/s00262-020-02545-4</identifier><identifier>PMID: 32170377</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Adaptive immunity ; Adult ; Aged ; Biomarkers, Tumor - genetics ; Cancer Research ; Cervical cancer ; Cervix ; Chemokines ; Cohort Studies ; CXCR2 protein ; Female ; Follow-Up Studies ; Granulocyte-Macrophage Colony-Stimulating Factor - genetics ; Humans ; Immune response ; Immunology ; Infiltration ; Leukocytosis ; Leukocytosis - etiology ; Leukocytosis - metabolism ; Leukocytosis - pathology ; Lymphocytes ; Lymphocytes, Tumor-Infiltrating - immunology ; Macrophages ; Macrophages - immunology ; Male ; Medicine ; Medicine & Public Health ; Metastases ; Middle Aged ; Neoplasms - complications ; Oncology ; Original ; Original Article ; Prognosis ; Radioresistance ; Receptors, Interleukin-8B - genetics ; Survival Rate ; Transcription ; Transcriptome ; Tumor Microenvironment - immunology ; Tumors ; Wound healing</subject><ispartof>Cancer Immunology, Immunotherapy, 2020-07, Vol.69 (7), p.1265-1277</ispartof><rights>Springer-Verlag GmbH Germany, part of Springer Nature 2020</rights><rights>Springer-Verlag GmbH Germany, part of Springer Nature 2020.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c431t-7ff0402356926b9b762406de12377654c1a4fa4e1ec2bbe2d53fa682fa050923</citedby><cites>FETCH-LOGICAL-c431t-7ff0402356926b9b762406de12377654c1a4fa4e1ec2bbe2d53fa682fa050923</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11027728/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11027728/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,315,728,781,785,886,27925,27926,41489,42558,51320,53792,53794</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32170377$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kim, Kyung Hwan</creatorcontrib><creatorcontrib>Sim, Nam Suk</creatorcontrib><creatorcontrib>Chang, Jee Suk</creatorcontrib><creatorcontrib>Kim, Yong Bae</creatorcontrib><title>Tumor immune microenvironment in cancer patients with leukocytosis</title><title>Cancer Immunology, Immunotherapy</title><addtitle>Cancer Immunol Immunother</addtitle><addtitle>Cancer Immunol Immunother</addtitle><description>Tumor-related leukocytosis (TRL) is correlated with poor survival in various types of cancers, but the microenvironment of TRL-associated human tumors has not been fully elucidated. Here, we aimed to characterize the immune microenvironment of cancer patients with TRL. The transcriptional signatures of tumor tissues obtained from cervical cancer patients with (TRL
pos
) and without TRL (TRL
neg
) were compared. As a surrogate for TRL diagnosis, a leukocytosis signature (LS) score was derived using genes differentially expressed between TRL
pos
and TRL
neg
tumors. The immunological profiles of patients in the TCGA database with high (LS
high
) or low LS scores were compared. TRL
pos
tumors were transcriptionally distinct from TRL
neg
tumors, exhibiting up-regulation of radioresistance and down-regulation of adaptive immune response-related genes. In the TCGA cervical cancer cohort (
n
= 303), patients with high LS had inferior survival rates compared to those with low LS (
P
= 0.023). LS
high
tumors were enriched in radioresistance, wound healing, and myeloid-derived suppressor cell (MDSC) signatures and had a higher infiltration of M2 macrophages and a lower infiltration of M1 macrophages and lymphocytes. LS
high
tumors also expressed higher levels of CXCR2 chemokines,
CSF2
, and
CSF3
. In the pan-cancer cohort (
n
= 9984), LS
high
tumors also exhibited poor survival, signatures of a suppressive immune microenvironment, and higher expression of CXCR2 chemokines. Our data provide evidence for a suppressive immune microenvironment in patients with TRL and suggest promising targets, such as the CXCR2 axis, for its therapeutic intervention.</description><subject>Adaptive immunity</subject><subject>Adult</subject><subject>Aged</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Cancer Research</subject><subject>Cervical cancer</subject><subject>Cervix</subject><subject>Chemokines</subject><subject>Cohort Studies</subject><subject>CXCR2 protein</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Granulocyte-Macrophage Colony-Stimulating Factor - genetics</subject><subject>Humans</subject><subject>Immune response</subject><subject>Immunology</subject><subject>Infiltration</subject><subject>Leukocytosis</subject><subject>Leukocytosis - etiology</subject><subject>Leukocytosis - metabolism</subject><subject>Leukocytosis - pathology</subject><subject>Lymphocytes</subject><subject>Lymphocytes, Tumor-Infiltrating - immunology</subject><subject>Macrophages</subject><subject>Macrophages - immunology</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Metastases</subject><subject>Middle Aged</subject><subject>Neoplasms - complications</subject><subject>Oncology</subject><subject>Original</subject><subject>Original Article</subject><subject>Prognosis</subject><subject>Radioresistance</subject><subject>Receptors, Interleukin-8B - genetics</subject><subject>Survival Rate</subject><subject>Transcription</subject><subject>Transcriptome</subject><subject>Tumor Microenvironment - immunology</subject><subject>Tumors</subject><subject>Wound healing</subject><issn>0340-7004</issn><issn>1432-0851</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp9kUtP3DAUha2qCIbHH-iiitQNm9Dr69dkhQBRqITEZvaW43HAkNiDnQzi32M6PEoXXVi27v18fK4PId8oHFEA9TMDoMQaEMoSXNT8C5lRzkppLuhXMgPGoVYAfIfs5nxXDghNs012GFIFTKkZOV1MQ0yVH4YpuGrwNkUX1j7FMLgwVj5U1gTrUrUyoy-VXD368bbq3XQf7dMYs8_7ZKszfXYHr_seWfw6X5xd1lfXF7_PTq5qyxkda9V1wAGZkA3KtmmVRA5y6SgWI1JwSw3vDHfUWWxbh0vBOiPn2BkQ0CDbI8cb2dXUDm5pi5lker1KfjDpSUfj9edO8Lf6Jq41pYBK4bwoHL4qpPgwuTzqwWfr-t4EF6esX4wwwSiVBf3xD3oXpxTKeBo55UIqAaJQuKHKr-WcXPfuhoJ-iUhvItIlIv0nIs3Lpe9_z_F-5S2TArANkEsr3Lj08fZ_ZJ8BuGacaA</recordid><startdate>20200701</startdate><enddate>20200701</enddate><creator>Kim, Kyung Hwan</creator><creator>Sim, Nam Suk</creator><creator>Chang, Jee Suk</creator><creator>Kim, Yong Bae</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</general><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>7T5</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20200701</creationdate><title>Tumor immune microenvironment in cancer patients with leukocytosis</title><author>Kim, Kyung Hwan ; Sim, Nam Suk ; Chang, Jee Suk ; Kim, Yong Bae</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c431t-7ff0402356926b9b762406de12377654c1a4fa4e1ec2bbe2d53fa682fa050923</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Adaptive immunity</topic><topic>Adult</topic><topic>Aged</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Cancer Research</topic><topic>Cervical cancer</topic><topic>Cervix</topic><topic>Chemokines</topic><topic>Cohort Studies</topic><topic>CXCR2 protein</topic><topic>Female</topic><topic>Follow-Up Studies</topic><topic>Granulocyte-Macrophage Colony-Stimulating Factor - genetics</topic><topic>Humans</topic><topic>Immune response</topic><topic>Immunology</topic><topic>Infiltration</topic><topic>Leukocytosis</topic><topic>Leukocytosis - etiology</topic><topic>Leukocytosis - metabolism</topic><topic>Leukocytosis - pathology</topic><topic>Lymphocytes</topic><topic>Lymphocytes, Tumor-Infiltrating - immunology</topic><topic>Macrophages</topic><topic>Macrophages - immunology</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Metastases</topic><topic>Middle Aged</topic><topic>Neoplasms - complications</topic><topic>Oncology</topic><topic>Original</topic><topic>Original Article</topic><topic>Prognosis</topic><topic>Radioresistance</topic><topic>Receptors, Interleukin-8B - genetics</topic><topic>Survival Rate</topic><topic>Transcription</topic><topic>Transcriptome</topic><topic>Tumor Microenvironment - immunology</topic><topic>Tumors</topic><topic>Wound healing</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kim, Kyung Hwan</creatorcontrib><creatorcontrib>Sim, Nam Suk</creatorcontrib><creatorcontrib>Chang, Jee Suk</creatorcontrib><creatorcontrib>Kim, Yong Bae</creatorcontrib><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>Immunology Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancer Immunology, Immunotherapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kim, Kyung Hwan</au><au>Sim, Nam Suk</au><au>Chang, Jee Suk</au><au>Kim, Yong Bae</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Tumor immune microenvironment in cancer patients with leukocytosis</atitle><jtitle>Cancer Immunology, Immunotherapy</jtitle><stitle>Cancer Immunol Immunother</stitle><addtitle>Cancer Immunol Immunother</addtitle><date>2020-07-01</date><risdate>2020</risdate><volume>69</volume><issue>7</issue><spage>1265</spage><epage>1277</epage><pages>1265-1277</pages><issn>0340-7004</issn><eissn>1432-0851</eissn><abstract>Tumor-related leukocytosis (TRL) is correlated with poor survival in various types of cancers, but the microenvironment of TRL-associated human tumors has not been fully elucidated. Here, we aimed to characterize the immune microenvironment of cancer patients with TRL. The transcriptional signatures of tumor tissues obtained from cervical cancer patients with (TRL
pos
) and without TRL (TRL
neg
) were compared. As a surrogate for TRL diagnosis, a leukocytosis signature (LS) score was derived using genes differentially expressed between TRL
pos
and TRL
neg
tumors. The immunological profiles of patients in the TCGA database with high (LS
high
) or low LS scores were compared. TRL
pos
tumors were transcriptionally distinct from TRL
neg
tumors, exhibiting up-regulation of radioresistance and down-regulation of adaptive immune response-related genes. In the TCGA cervical cancer cohort (
n
= 303), patients with high LS had inferior survival rates compared to those with low LS (
P
= 0.023). LS
high
tumors were enriched in radioresistance, wound healing, and myeloid-derived suppressor cell (MDSC) signatures and had a higher infiltration of M2 macrophages and a lower infiltration of M1 macrophages and lymphocytes. LS
high
tumors also expressed higher levels of CXCR2 chemokines,
CSF2
, and
CSF3
. In the pan-cancer cohort (
n
= 9984), LS
high
tumors also exhibited poor survival, signatures of a suppressive immune microenvironment, and higher expression of CXCR2 chemokines. Our data provide evidence for a suppressive immune microenvironment in patients with TRL and suggest promising targets, such as the CXCR2 axis, for its therapeutic intervention.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>32170377</pmid><doi>10.1007/s00262-020-02545-4</doi><tpages>13</tpages></addata></record> |
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| identifier | ISSN: 0340-7004 |
| ispartof | Cancer Immunology, Immunotherapy, 2020-07, Vol.69 (7), p.1265-1277 |
| issn | 0340-7004 1432-0851 |
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| source | MEDLINE; SpringerNature Journals; PubMed Central |
| subjects | Adaptive immunity Adult Aged Biomarkers, Tumor - genetics Cancer Research Cervical cancer Cervix Chemokines Cohort Studies CXCR2 protein Female Follow-Up Studies Granulocyte-Macrophage Colony-Stimulating Factor - genetics Humans Immune response Immunology Infiltration Leukocytosis Leukocytosis - etiology Leukocytosis - metabolism Leukocytosis - pathology Lymphocytes Lymphocytes, Tumor-Infiltrating - immunology Macrophages Macrophages - immunology Male Medicine Medicine & Public Health Metastases Middle Aged Neoplasms - complications Oncology Original Original Article Prognosis Radioresistance Receptors, Interleukin-8B - genetics Survival Rate Transcription Transcriptome Tumor Microenvironment - immunology Tumors Wound healing |
| title | Tumor immune microenvironment in cancer patients with leukocytosis |
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