Beyond PD-L1-Identification of Further Potential Therapeutic Targets in Oral Cancer
The involvement of immune cell infiltration and immune regulation in the progression of oral squamous cell carcinoma (OSCC) is shown. Anti-PD-1 therapy is approved for the treatment of advanced OSCC cases, but not all patients respond to immune checkpoint inhibitors. Hence, further targets for thera...
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| Veröffentlicht in: | Cancers 2022-04, Vol.14 (7), p.1812 |
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| creator | Weber, Manuel Lutz, Rainer Olmos, Manuel Glajzer, Jacek Baran, Christoph Nobis, Christopher-Philipp Möst, Tobias Eckstein, Markus Kesting, Marco Ries, Jutta |
| description | The involvement of immune cell infiltration and immune regulation in the progression of oral squamous cell carcinoma (OSCC) is shown. Anti-PD-1 therapy is approved for the treatment of advanced OSCC cases, but not all patients respond to immune checkpoint inhibitors. Hence, further targets for therapeutic approaches are needed. The number of identified cellular receptors with immune checkpoint function is constantly increasing. This study aimed to perform a comparative analysis of a large number of immune checkpoints in OSCC in order to identify possible targets for therapeutic application.
A NanoString mRNA analysis was performed to assess the expression levels of 21 immune regulatory checkpoint molecules in OSCC tissue (
= 98) and healthy oral mucosa (NOM;
= 41). The expression rates were compared between the two groups, and their association with prognostic parameters was determined. Additionally, relevant correlations between the expression levels of different checkpoints were examined.
In OSCC tissue, significantly increased expression of CD115, CD163, CD68, CD86, CD96, GITRL, CD28 and PD-L1 was detected. Additionally, a marginally significant increase in CD8 expression was observed. BTLA and PD-1 levels were substantially increased, but the differential expression was not statistically significant. The expression of CD137L was significantly downregulated in OSCC compared to NOM. Correlations between immune checkpoint expression levels were demonstrated, and some occurred specifically in OSCC tissue.
The upregulation of inhibitory receptors and ligands and the downregulation of activators could contribute to reduced effector T-cell function and could induce local immunosuppression in OSCC. Increased expression of activating actors of the immune system could be explained by the increased infiltration of myeloid cells and T-cells in OSCC tissue. The analysis contributes to the understanding of immune escape in OSCC and reveals potential targets for oral cancer immunotherapy. |
| doi_str_mv | 10.3390/cancers14071812 |
| format | Article |
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A NanoString mRNA analysis was performed to assess the expression levels of 21 immune regulatory checkpoint molecules in OSCC tissue (
= 98) and healthy oral mucosa (NOM;
= 41). The expression rates were compared between the two groups, and their association with prognostic parameters was determined. Additionally, relevant correlations between the expression levels of different checkpoints were examined.
In OSCC tissue, significantly increased expression of CD115, CD163, CD68, CD86, CD96, GITRL, CD28 and PD-L1 was detected. Additionally, a marginally significant increase in CD8 expression was observed. BTLA and PD-1 levels were substantially increased, but the differential expression was not statistically significant. The expression of CD137L was significantly downregulated in OSCC compared to NOM. Correlations between immune checkpoint expression levels were demonstrated, and some occurred specifically in OSCC tissue.
The upregulation of inhibitory receptors and ligands and the downregulation of activators could contribute to reduced effector T-cell function and could induce local immunosuppression in OSCC. Increased expression of activating actors of the immune system could be explained by the increased infiltration of myeloid cells and T-cells in OSCC tissue. The analysis contributes to the understanding of immune escape in OSCC and reveals potential targets for oral cancer immunotherapy.</description><identifier>ISSN: 2072-6694</identifier><identifier>EISSN: 2072-6694</identifier><identifier>DOI: 10.3390/cancers14071812</identifier><identifier>PMID: 35406584</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Antigens ; BTLA protein ; Cancer immunotherapy ; Cancer therapies ; CD163 antigen ; CD28 antigen ; CD8 antigen ; CD86 antigen ; Comparative analysis ; Cytokines ; Fibroblasts ; Immune checkpoint ; Immune system ; Immunoglobulins ; Immunomodulation ; Immunoregulation ; Immunosuppression ; Immunotherapy ; Infiltration ; Ligands ; Lymphocytes ; Lymphocytes T ; Medical prognosis ; Metastases ; mRNA ; Mucosa ; Myeloid cells ; Oral cancer ; Oral carcinoma ; Oral squamous cell carcinoma ; Patients ; PD-1 protein ; PD-L1 protein ; Receptor mechanisms ; Statistical analysis ; Surgery ; Tumors</subject><ispartof>Cancers, 2022-04, Vol.14 (7), p.1812</ispartof><rights>2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2022 by the authors. 2022</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c421t-9bc7a1194d332ea6b3aa14c7769e07da0d2c3dbcbfc7da1cf912afeabca91c453</citedby><cites>FETCH-LOGICAL-c421t-9bc7a1194d332ea6b3aa14c7769e07da0d2c3dbcbfc7da1cf912afeabca91c453</cites><orcidid>0000-0002-8649-5977 ; 0000-0001-5778-2742 ; 0000-0003-0199-9437 ; 0000-0003-2262-102X</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/PMC8997752/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8997752/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35406584$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Weber, Manuel</creatorcontrib><creatorcontrib>Lutz, Rainer</creatorcontrib><creatorcontrib>Olmos, Manuel</creatorcontrib><creatorcontrib>Glajzer, Jacek</creatorcontrib><creatorcontrib>Baran, Christoph</creatorcontrib><creatorcontrib>Nobis, Christopher-Philipp</creatorcontrib><creatorcontrib>Möst, Tobias</creatorcontrib><creatorcontrib>Eckstein, Markus</creatorcontrib><creatorcontrib>Kesting, Marco</creatorcontrib><creatorcontrib>Ries, Jutta</creatorcontrib><title>Beyond PD-L1-Identification of Further Potential Therapeutic Targets in Oral Cancer</title><title>Cancers</title><addtitle>Cancers (Basel)</addtitle><description>The involvement of immune cell infiltration and immune regulation in the progression of oral squamous cell carcinoma (OSCC) is shown. Anti-PD-1 therapy is approved for the treatment of advanced OSCC cases, but not all patients respond to immune checkpoint inhibitors. Hence, further targets for therapeutic approaches are needed. The number of identified cellular receptors with immune checkpoint function is constantly increasing. This study aimed to perform a comparative analysis of a large number of immune checkpoints in OSCC in order to identify possible targets for therapeutic application.
A NanoString mRNA analysis was performed to assess the expression levels of 21 immune regulatory checkpoint molecules in OSCC tissue (
= 98) and healthy oral mucosa (NOM;
= 41). The expression rates were compared between the two groups, and their association with prognostic parameters was determined. Additionally, relevant correlations between the expression levels of different checkpoints were examined.
In OSCC tissue, significantly increased expression of CD115, CD163, CD68, CD86, CD96, GITRL, CD28 and PD-L1 was detected. Additionally, a marginally significant increase in CD8 expression was observed. BTLA and PD-1 levels were substantially increased, but the differential expression was not statistically significant. The expression of CD137L was significantly downregulated in OSCC compared to NOM. Correlations between immune checkpoint expression levels were demonstrated, and some occurred specifically in OSCC tissue.
The upregulation of inhibitory receptors and ligands and the downregulation of activators could contribute to reduced effector T-cell function and could induce local immunosuppression in OSCC. Increased expression of activating actors of the immune system could be explained by the increased infiltration of myeloid cells and T-cells in OSCC tissue. The analysis contributes to the understanding of immune escape in OSCC and reveals potential targets for oral cancer immunotherapy.</description><subject>Antigens</subject><subject>BTLA protein</subject><subject>Cancer immunotherapy</subject><subject>Cancer therapies</subject><subject>CD163 antigen</subject><subject>CD28 antigen</subject><subject>CD8 antigen</subject><subject>CD86 antigen</subject><subject>Comparative analysis</subject><subject>Cytokines</subject><subject>Fibroblasts</subject><subject>Immune checkpoint</subject><subject>Immune system</subject><subject>Immunoglobulins</subject><subject>Immunomodulation</subject><subject>Immunoregulation</subject><subject>Immunosuppression</subject><subject>Immunotherapy</subject><subject>Infiltration</subject><subject>Ligands</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Medical prognosis</subject><subject>Metastases</subject><subject>mRNA</subject><subject>Mucosa</subject><subject>Myeloid cells</subject><subject>Oral cancer</subject><subject>Oral carcinoma</subject><subject>Oral squamous cell carcinoma</subject><subject>Patients</subject><subject>PD-1 protein</subject><subject>PD-L1 protein</subject><subject>Receptor mechanisms</subject><subject>Statistical analysis</subject><subject>Surgery</subject><subject>Tumors</subject><issn>2072-6694</issn><issn>2072-6694</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpdkc1LAzEUxIMoVtSzN1nw4mVtvjbZXAStVgsFBes5vM1ma6Td1GRX6H9vqlXUXJLH_DLMYxA6IfiCMYWHBlpjQyQcS1ISuoMOKJY0F0Lx3V_vATqO8RWnwxiRQu6jASs4FkXJD9DTtV37ts4eb_IpySe1bTvXOAOd823mm2zch-7FhuzRdxsJFtksjbCyfedMNoMwt13MXJs9hKSNPhMdob0GFtEeb-9D9Dy-nY3u8-nD3WR0Nc0Np6TLVWUkEKJ4zRi1ICoGQLiRUiiLZQ24pobVlakakyZiGkUoNBYqA4oYXrBDdPnlu-qrpa1NCphC6FVwSwhr7cHpv0rrXvTcv-tSKSkLmgzOtwbBv_U2dnrporGLBbTW91FTwVWhaKnKhJ79Q199H9q03oYqlWBUsEQNvygTfIzBNj9hCNabzvS_ztKP0987_PDfDbEPu1GU0g</recordid><startdate>20220402</startdate><enddate>20220402</enddate><creator>Weber, Manuel</creator><creator>Lutz, Rainer</creator><creator>Olmos, Manuel</creator><creator>Glajzer, Jacek</creator><creator>Baran, Christoph</creator><creator>Nobis, Christopher-Philipp</creator><creator>Möst, Tobias</creator><creator>Eckstein, Markus</creator><creator>Kesting, Marco</creator><creator>Ries, Jutta</creator><general>MDPI AG</general><general>MDPI</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T5</scope><scope>7TO</scope><scope>7XB</scope><scope>8FE</scope><scope>8FH</scope><scope>8FK</scope><scope>8G5</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>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-8649-5977</orcidid><orcidid>https://orcid.org/0000-0001-5778-2742</orcidid><orcidid>https://orcid.org/0000-0003-0199-9437</orcidid><orcidid>https://orcid.org/0000-0003-2262-102X</orcidid></search><sort><creationdate>20220402</creationdate><title>Beyond PD-L1-Identification of Further Potential Therapeutic Targets in Oral Cancer</title><author>Weber, Manuel ; 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Anti-PD-1 therapy is approved for the treatment of advanced OSCC cases, but not all patients respond to immune checkpoint inhibitors. Hence, further targets for therapeutic approaches are needed. The number of identified cellular receptors with immune checkpoint function is constantly increasing. This study aimed to perform a comparative analysis of a large number of immune checkpoints in OSCC in order to identify possible targets for therapeutic application.
A NanoString mRNA analysis was performed to assess the expression levels of 21 immune regulatory checkpoint molecules in OSCC tissue (
= 98) and healthy oral mucosa (NOM;
= 41). The expression rates were compared between the two groups, and their association with prognostic parameters was determined. Additionally, relevant correlations between the expression levels of different checkpoints were examined.
In OSCC tissue, significantly increased expression of CD115, CD163, CD68, CD86, CD96, GITRL, CD28 and PD-L1 was detected. Additionally, a marginally significant increase in CD8 expression was observed. BTLA and PD-1 levels were substantially increased, but the differential expression was not statistically significant. The expression of CD137L was significantly downregulated in OSCC compared to NOM. Correlations between immune checkpoint expression levels were demonstrated, and some occurred specifically in OSCC tissue.
The upregulation of inhibitory receptors and ligands and the downregulation of activators could contribute to reduced effector T-cell function and could induce local immunosuppression in OSCC. Increased expression of activating actors of the immune system could be explained by the increased infiltration of myeloid cells and T-cells in OSCC tissue. The analysis contributes to the understanding of immune escape in OSCC and reveals potential targets for oral cancer immunotherapy.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>35406584</pmid><doi>10.3390/cancers14071812</doi><orcidid>https://orcid.org/0000-0002-8649-5977</orcidid><orcidid>https://orcid.org/0000-0001-5778-2742</orcidid><orcidid>https://orcid.org/0000-0003-0199-9437</orcidid><orcidid>https://orcid.org/0000-0003-2262-102X</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Antigens BTLA protein Cancer immunotherapy Cancer therapies CD163 antigen CD28 antigen CD8 antigen CD86 antigen Comparative analysis Cytokines Fibroblasts Immune checkpoint Immune system Immunoglobulins Immunomodulation Immunoregulation Immunosuppression Immunotherapy Infiltration Ligands Lymphocytes Lymphocytes T Medical prognosis Metastases mRNA Mucosa Myeloid cells Oral cancer Oral carcinoma Oral squamous cell carcinoma Patients PD-1 protein PD-L1 protein Receptor mechanisms Statistical analysis Surgery Tumors |
| title | Beyond PD-L1-Identification of Further Potential Therapeutic Targets in Oral Cancer |
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