High abundance of Lachnospiraceae in the human gut microbiome is related to high immunoscores in advanced colorectal cancer

Introduction The tumor microenvironment (TME) in colorectal cancer (CRC) includes the gut microbiome, immune cells, angiogenic factors, and fibroblasts and plays a major role in cancer progression. The Immunoscore (IS) is based on tumor infiltration by immune cells that are known prognostic biomarke...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Cancer Immunology, Immunotherapy Immunotherapy, 2023-02, Vol.72 (2), p.315-326
Hauptverfasser: Hexun, Zhang, Miyake, Toru, Maekawa, Takeru, Mori, Haruki, Yasukawa, Daiki, Ohno, Masashi, Nishida, Atsushi, Andoh, Akira, Tani, Masaji
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 326
container_issue 2
container_start_page 315
container_title Cancer Immunology, Immunotherapy
container_volume 72
creator Hexun, Zhang
Miyake, Toru
Maekawa, Takeru
Mori, Haruki
Yasukawa, Daiki
Ohno, Masashi
Nishida, Atsushi
Andoh, Akira
Tani, Masaji
description Introduction The tumor microenvironment (TME) in colorectal cancer (CRC) includes the gut microbiome, immune cells, angiogenic factors, and fibroblasts and plays a major role in cancer progression. The Immunoscore (IS) is based on tumor infiltration by immune cells that are known prognostic biomarkers for CRC. However, the interrelation between the IS, microbiome, and other TME factors in human CRC remains unclear. Patients and methods A cohort of 94 patients with CRC was examined at the Shiga University of Medical Science Hospital in Japan. The expression levels of CD3, CD8, CD31, and alpha-smooth muscle actin (α-SMA) in the primary tumor were evaluated by immunohistochemistry. The IS was calculated based on the results of the CD3 and CD8 staining assays. Microbiomes in patients with CRC were examined by amplicon sequencing. Results The expression levels of α-SMA and tumor-infiltrating lymphocytes in patients with CRC were negatively correlated ( P  = 0.006). A high IS was associated with high abundance of Lachnospiraceae in the microbiomes of patients with CRC. Conclusion Lymphocyte infiltration into the primary tumor was marked by reduced density of cancer-associated fibroblasts and enrichment of the Lachnospiraceae family in the gut microbiome, which may influence CRC progression.
doi_str_mv 10.1007/s00262-022-03256-8
format Article
fullrecord <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_10991469</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2693771927</sourcerecordid><originalsourceid>FETCH-LOGICAL-c515t-d71c7bcf563dedc9afd97a19ea2e11f2196fac0ed53a87f88effbff14f1e8b133</originalsourceid><addsrcrecordid>eNp9UcuO1DAQtBCIHQZ-gAOyxIVLwI8kdk4IrYBFGokLnK2O0554ldiDnay04udxmGV5HDhYdndXlbu7CHnO2WvOmHqTGROtqJgoR4qmrfQDsuO1LKFu-EOyY7JmlWKsviBPcr4uD8G67jG5kI1uOyn1jny_8seRQr-GAYJFGh09gB1DzCefwCIg9YEuI9JxnSHQ47rQ2dsUex_nUss04QQLDnSJdNy0_DyvhW5jwrxxYbjZlAdq41RydoGJ2i2TnpJHDqaMz-7uPfn64f2Xy6vq8Pnjp8t3h8o2vFmqQXGreuuaVg442A7c0CngHYJAzp3gXevAMhwaCVo5rdG53jleO46651Luyduz7mnt56KAYUkwmVPyM6RbE8GbvyvBj-YYbwwv2-J12dSevLpTSPHbinkxs88WpwkCxjUbUTBK8U6oAn35D_Q6rimU-YxQrW404-3WkjijyiZzTujuu-HMbOaas7mmmGt-mmt0Ib34c457yi83C0CeAbmUwhHT77__I_sDBdGzZQ</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2768580163</pqid></control><display><type>article</type><title>High abundance of Lachnospiraceae in the human gut microbiome is related to high immunoscores in advanced colorectal cancer</title><source>MEDLINE</source><source>Springer Nature - Complete Springer Journals</source><source>PubMed Central</source><creator>Hexun, Zhang ; Miyake, Toru ; Maekawa, Takeru ; Mori, Haruki ; Yasukawa, Daiki ; Ohno, Masashi ; Nishida, Atsushi ; Andoh, Akira ; Tani, Masaji</creator><creatorcontrib>Hexun, Zhang ; Miyake, Toru ; Maekawa, Takeru ; Mori, Haruki ; Yasukawa, Daiki ; Ohno, Masashi ; Nishida, Atsushi ; Andoh, Akira ; Tani, Masaji</creatorcontrib><description>Introduction The tumor microenvironment (TME) in colorectal cancer (CRC) includes the gut microbiome, immune cells, angiogenic factors, and fibroblasts and plays a major role in cancer progression. The Immunoscore (IS) is based on tumor infiltration by immune cells that are known prognostic biomarkers for CRC. However, the interrelation between the IS, microbiome, and other TME factors in human CRC remains unclear. Patients and methods A cohort of 94 patients with CRC was examined at the Shiga University of Medical Science Hospital in Japan. The expression levels of CD3, CD8, CD31, and alpha-smooth muscle actin (α-SMA) in the primary tumor were evaluated by immunohistochemistry. The IS was calculated based on the results of the CD3 and CD8 staining assays. Microbiomes in patients with CRC were examined by amplicon sequencing. Results The expression levels of α-SMA and tumor-infiltrating lymphocytes in patients with CRC were negatively correlated ( P  = 0.006). A high IS was associated with high abundance of Lachnospiraceae in the microbiomes of patients with CRC. Conclusion Lymphocyte infiltration into the primary tumor was marked by reduced density of cancer-associated fibroblasts and enrichment of the Lachnospiraceae family in the gut microbiome, which may influence CRC progression.</description><identifier>ISSN: 0340-7004</identifier><identifier>ISSN: 1432-0851</identifier><identifier>EISSN: 1432-0851</identifier><identifier>DOI: 10.1007/s00262-022-03256-8</identifier><identifier>PMID: 35869338</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Actin ; Angiogenesis ; Cancer ; Cancer Research ; CD3 antigen ; CD8 antigen ; Colorectal cancer ; Colorectal carcinoma ; Colorectal Neoplasms - pathology ; Digestive system ; Fibroblasts ; Fibroblasts - metabolism ; Gastrointestinal Microbiome ; Humans ; Immunohistochemistry ; Immunology ; Infiltration ; Intestinal microflora ; Lachnospiraceae ; Lymphocytes ; Lymphocytes, Tumor-Infiltrating ; Medicine ; Medicine &amp; Public Health ; Metastases ; Microbiomes ; Microbiota ; Oncology ; Original ; Original Article ; Patients ; Prognosis ; Smooth muscle ; Tumor Microenvironment ; Tumor-infiltrating lymphocytes</subject><ispartof>Cancer Immunology, Immunotherapy, 2023-02, Vol.72 (2), p.315-326</ispartof><rights>The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2022</rights><rights>2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.</rights><rights>The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2022.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c515t-d71c7bcf563dedc9afd97a19ea2e11f2196fac0ed53a87f88effbff14f1e8b133</citedby><cites>FETCH-LOGICAL-c515t-d71c7bcf563dedc9afd97a19ea2e11f2196fac0ed53a87f88effbff14f1e8b133</cites><orcidid>0000-0003-0947-0116</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/PMC10991469/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10991469/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,41464,42533,51294,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35869338$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hexun, Zhang</creatorcontrib><creatorcontrib>Miyake, Toru</creatorcontrib><creatorcontrib>Maekawa, Takeru</creatorcontrib><creatorcontrib>Mori, Haruki</creatorcontrib><creatorcontrib>Yasukawa, Daiki</creatorcontrib><creatorcontrib>Ohno, Masashi</creatorcontrib><creatorcontrib>Nishida, Atsushi</creatorcontrib><creatorcontrib>Andoh, Akira</creatorcontrib><creatorcontrib>Tani, Masaji</creatorcontrib><title>High abundance of Lachnospiraceae in the human gut microbiome is related to high immunoscores in advanced colorectal cancer</title><title>Cancer Immunology, Immunotherapy</title><addtitle>Cancer Immunol Immunother</addtitle><addtitle>Cancer Immunol Immunother</addtitle><description>Introduction The tumor microenvironment (TME) in colorectal cancer (CRC) includes the gut microbiome, immune cells, angiogenic factors, and fibroblasts and plays a major role in cancer progression. The Immunoscore (IS) is based on tumor infiltration by immune cells that are known prognostic biomarkers for CRC. However, the interrelation between the IS, microbiome, and other TME factors in human CRC remains unclear. Patients and methods A cohort of 94 patients with CRC was examined at the Shiga University of Medical Science Hospital in Japan. The expression levels of CD3, CD8, CD31, and alpha-smooth muscle actin (α-SMA) in the primary tumor were evaluated by immunohistochemistry. The IS was calculated based on the results of the CD3 and CD8 staining assays. Microbiomes in patients with CRC were examined by amplicon sequencing. Results The expression levels of α-SMA and tumor-infiltrating lymphocytes in patients with CRC were negatively correlated ( P  = 0.006). A high IS was associated with high abundance of Lachnospiraceae in the microbiomes of patients with CRC. Conclusion Lymphocyte infiltration into the primary tumor was marked by reduced density of cancer-associated fibroblasts and enrichment of the Lachnospiraceae family in the gut microbiome, which may influence CRC progression.</description><subject>Actin</subject><subject>Angiogenesis</subject><subject>Cancer</subject><subject>Cancer Research</subject><subject>CD3 antigen</subject><subject>CD8 antigen</subject><subject>Colorectal cancer</subject><subject>Colorectal carcinoma</subject><subject>Colorectal Neoplasms - pathology</subject><subject>Digestive system</subject><subject>Fibroblasts</subject><subject>Fibroblasts - metabolism</subject><subject>Gastrointestinal Microbiome</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Immunology</subject><subject>Infiltration</subject><subject>Intestinal microflora</subject><subject>Lachnospiraceae</subject><subject>Lymphocytes</subject><subject>Lymphocytes, Tumor-Infiltrating</subject><subject>Medicine</subject><subject>Medicine &amp; Public Health</subject><subject>Metastases</subject><subject>Microbiomes</subject><subject>Microbiota</subject><subject>Oncology</subject><subject>Original</subject><subject>Original Article</subject><subject>Patients</subject><subject>Prognosis</subject><subject>Smooth muscle</subject><subject>Tumor Microenvironment</subject><subject>Tumor-infiltrating lymphocytes</subject><issn>0340-7004</issn><issn>1432-0851</issn><issn>1432-0851</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp9UcuO1DAQtBCIHQZ-gAOyxIVLwI8kdk4IrYBFGokLnK2O0554ldiDnay04udxmGV5HDhYdndXlbu7CHnO2WvOmHqTGROtqJgoR4qmrfQDsuO1LKFu-EOyY7JmlWKsviBPcr4uD8G67jG5kI1uOyn1jny_8seRQr-GAYJFGh09gB1DzCefwCIg9YEuI9JxnSHQ47rQ2dsUex_nUss04QQLDnSJdNy0_DyvhW5jwrxxYbjZlAdq41RydoGJ2i2TnpJHDqaMz-7uPfn64f2Xy6vq8Pnjp8t3h8o2vFmqQXGreuuaVg442A7c0CngHYJAzp3gXevAMhwaCVo5rdG53jleO46651Luyduz7mnt56KAYUkwmVPyM6RbE8GbvyvBj-YYbwwv2-J12dSevLpTSPHbinkxs88WpwkCxjUbUTBK8U6oAn35D_Q6rimU-YxQrW404-3WkjijyiZzTujuu-HMbOaas7mmmGt-mmt0Ib34c457yi83C0CeAbmUwhHT77__I_sDBdGzZQ</recordid><startdate>20230201</startdate><enddate>20230201</enddate><creator>Hexun, Zhang</creator><creator>Miyake, Toru</creator><creator>Maekawa, Takeru</creator><creator>Mori, Haruki</creator><creator>Yasukawa, Daiki</creator><creator>Ohno, Masashi</creator><creator>Nishida, Atsushi</creator><creator>Andoh, Akira</creator><creator>Tani, Masaji</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><orcidid>https://orcid.org/0000-0003-0947-0116</orcidid></search><sort><creationdate>20230201</creationdate><title>High abundance of Lachnospiraceae in the human gut microbiome is related to high immunoscores in advanced colorectal cancer</title><author>Hexun, Zhang ; Miyake, Toru ; Maekawa, Takeru ; Mori, Haruki ; Yasukawa, Daiki ; Ohno, Masashi ; Nishida, Atsushi ; Andoh, Akira ; Tani, Masaji</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c515t-d71c7bcf563dedc9afd97a19ea2e11f2196fac0ed53a87f88effbff14f1e8b133</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Actin</topic><topic>Angiogenesis</topic><topic>Cancer</topic><topic>Cancer Research</topic><topic>CD3 antigen</topic><topic>CD8 antigen</topic><topic>Colorectal cancer</topic><topic>Colorectal carcinoma</topic><topic>Colorectal Neoplasms - pathology</topic><topic>Digestive system</topic><topic>Fibroblasts</topic><topic>Fibroblasts - metabolism</topic><topic>Gastrointestinal Microbiome</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Immunology</topic><topic>Infiltration</topic><topic>Intestinal microflora</topic><topic>Lachnospiraceae</topic><topic>Lymphocytes</topic><topic>Lymphocytes, Tumor-Infiltrating</topic><topic>Medicine</topic><topic>Medicine &amp; Public Health</topic><topic>Metastases</topic><topic>Microbiomes</topic><topic>Microbiota</topic><topic>Oncology</topic><topic>Original</topic><topic>Original Article</topic><topic>Patients</topic><topic>Prognosis</topic><topic>Smooth muscle</topic><topic>Tumor Microenvironment</topic><topic>Tumor-infiltrating lymphocytes</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hexun, Zhang</creatorcontrib><creatorcontrib>Miyake, Toru</creatorcontrib><creatorcontrib>Maekawa, Takeru</creatorcontrib><creatorcontrib>Mori, Haruki</creatorcontrib><creatorcontrib>Yasukawa, Daiki</creatorcontrib><creatorcontrib>Ohno, Masashi</creatorcontrib><creatorcontrib>Nishida, Atsushi</creatorcontrib><creatorcontrib>Andoh, Akira</creatorcontrib><creatorcontrib>Tani, Masaji</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 &amp; 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 &amp; Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health &amp; 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>Hexun, Zhang</au><au>Miyake, Toru</au><au>Maekawa, Takeru</au><au>Mori, Haruki</au><au>Yasukawa, Daiki</au><au>Ohno, Masashi</au><au>Nishida, Atsushi</au><au>Andoh, Akira</au><au>Tani, Masaji</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>High abundance of Lachnospiraceae in the human gut microbiome is related to high immunoscores in advanced colorectal cancer</atitle><jtitle>Cancer Immunology, Immunotherapy</jtitle><stitle>Cancer Immunol Immunother</stitle><addtitle>Cancer Immunol Immunother</addtitle><date>2023-02-01</date><risdate>2023</risdate><volume>72</volume><issue>2</issue><spage>315</spage><epage>326</epage><pages>315-326</pages><issn>0340-7004</issn><issn>1432-0851</issn><eissn>1432-0851</eissn><abstract>Introduction The tumor microenvironment (TME) in colorectal cancer (CRC) includes the gut microbiome, immune cells, angiogenic factors, and fibroblasts and plays a major role in cancer progression. The Immunoscore (IS) is based on tumor infiltration by immune cells that are known prognostic biomarkers for CRC. However, the interrelation between the IS, microbiome, and other TME factors in human CRC remains unclear. Patients and methods A cohort of 94 patients with CRC was examined at the Shiga University of Medical Science Hospital in Japan. The expression levels of CD3, CD8, CD31, and alpha-smooth muscle actin (α-SMA) in the primary tumor were evaluated by immunohistochemistry. The IS was calculated based on the results of the CD3 and CD8 staining assays. Microbiomes in patients with CRC were examined by amplicon sequencing. Results The expression levels of α-SMA and tumor-infiltrating lymphocytes in patients with CRC were negatively correlated ( P  = 0.006). A high IS was associated with high abundance of Lachnospiraceae in the microbiomes of patients with CRC. Conclusion Lymphocyte infiltration into the primary tumor was marked by reduced density of cancer-associated fibroblasts and enrichment of the Lachnospiraceae family in the gut microbiome, which may influence CRC progression.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>35869338</pmid><doi>10.1007/s00262-022-03256-8</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0003-0947-0116</orcidid><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 0340-7004
ispartof Cancer Immunology, Immunotherapy, 2023-02, Vol.72 (2), p.315-326
issn 0340-7004
1432-0851
1432-0851
language eng
recordid cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_10991469
source MEDLINE; Springer Nature - Complete Springer Journals; PubMed Central
subjects Actin
Angiogenesis
Cancer
Cancer Research
CD3 antigen
CD8 antigen
Colorectal cancer
Colorectal carcinoma
Colorectal Neoplasms - pathology
Digestive system
Fibroblasts
Fibroblasts - metabolism
Gastrointestinal Microbiome
Humans
Immunohistochemistry
Immunology
Infiltration
Intestinal microflora
Lachnospiraceae
Lymphocytes
Lymphocytes, Tumor-Infiltrating
Medicine
Medicine & Public Health
Metastases
Microbiomes
Microbiota
Oncology
Original
Original Article
Patients
Prognosis
Smooth muscle
Tumor Microenvironment
Tumor-infiltrating lymphocytes
title High abundance of Lachnospiraceae in the human gut microbiome is related to high immunoscores in advanced colorectal cancer
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-30T23%3A05%3A04IST&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=High%20abundance%20of%20Lachnospiraceae%20in%20the%20human%20gut%20microbiome%20is%20related%20to%20high%20immunoscores%20in%20advanced%20colorectal%20cancer&rft.jtitle=Cancer%20Immunology,%20Immunotherapy&rft.au=Hexun,%20Zhang&rft.date=2023-02-01&rft.volume=72&rft.issue=2&rft.spage=315&rft.epage=326&rft.pages=315-326&rft.issn=0340-7004&rft.eissn=1432-0851&rft_id=info:doi/10.1007/s00262-022-03256-8&rft_dat=%3Cproquest_pubme%3E2693771927%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=2768580163&rft_id=info:pmid/35869338&rfr_iscdi=true