T-Cell Receptor Profiling and Prognosis After Stereotactic Body Radiation Therapy For Stage I Non-Small-Cell Lung Cancer
Radiotherapy is known to influence immune function, including T cell receptor (TCR) repertoire. We evaluated the TCR repertoire before and after stereotactic body radiotherapy (SBRT) for stage I non-small-cell lung cancer (NSCLC) and explored correlations between TCR indexes and distant failure afte...
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| Veröffentlicht in: | Frontiers in immunology 2021-10, Vol.12, p.719285-719285, Article 719285 |
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| creator | Wu, Lirong Zhu, Jun Rudqvist, Nils-Petter Welsh, James Lee, Percy Liao, Zhongxing Xu, Ting Jiang, Ming Zhu, Xiangzhi Pan, Xuan Li, Pansong Zhou, Zhipeng He, Xia Yin, Rong Feng, Jifeng |
| description | Radiotherapy is known to influence immune function, including T cell receptor (TCR) repertoire. We evaluated the TCR repertoire before and after stereotactic body radiotherapy (SBRT) for stage I non-small-cell lung cancer (NSCLC) and explored correlations between TCR indexes and distant failure after SBRT. TCR repertoires were analyzed in peripheral blood mononuclear cells (PBMCs) collected before and after SBRT from 19 patients. TCR combinational diversity in V and J genes was assessed with multiplex PCR of genomic DNA from PBMCs and tested for associations with clinical response. All patients received definitive SBRT to a biologically effective dose of >=100 Gy. The number of unique TCR clones was decreased after SBRT versus before, but clonality and the Shannon Entropy did not change. Four patients (21%) developed distant metastases after SBRT (median 7 months); those patients had lower Shannon Entropy in post-SBRT samples than patients without metastasis. Patients with a low change in Shannon Entropy from before to after SBRT [(post-SBRT Shannon Entropy minus baseline Shannon)/(baseline Shannon) * 100] had poorer metastasis-free survival than those with high change in Shannon Entropy (P |
| doi_str_mv | 10.3389/fimmu.2021.719285 |
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We evaluated the TCR repertoire before and after stereotactic body radiotherapy (SBRT) for stage I non-small-cell lung cancer (NSCLC) and explored correlations between TCR indexes and distant failure after SBRT. TCR repertoires were analyzed in peripheral blood mononuclear cells (PBMCs) collected before and after SBRT from 19 patients. TCR combinational diversity in V and J genes was assessed with multiplex PCR of genomic DNA from PBMCs and tested for associations with clinical response. All patients received definitive SBRT to a biologically effective dose of >=100 Gy. The number of unique TCR clones was decreased after SBRT versus before, but clonality and the Shannon Entropy did not change. Four patients (21%) developed distant metastases after SBRT (median 7 months); those patients had lower Shannon Entropy in post-SBRT samples than patients without metastasis. Patients with a low change in Shannon Entropy from before to after SBRT [(post-SBRT Shannon Entropy minus baseline Shannon)/(baseline Shannon) * 100] had poorer metastasis-free survival than those with high change in Shannon Entropy (P<0.001). Frequencies in V/J gene fragment expression in the TCR beta chain were also different for patients with or without metastases (two V fragments in baseline samples and 2 J and 9 V fragments in post-treatment samples). This comprehensive analysis of immune status before and after SBRT showed that quantitative assessments of TCRs can help evaluate prognosis in early-stage NSCLC.</description><identifier>ISSN: 1664-3224</identifier><identifier>EISSN: 1664-3224</identifier><identifier>DOI: 10.3389/fimmu.2021.719285</identifier><identifier>PMID: 34733273</identifier><language>eng</language><publisher>LAUSANNE: Frontiers Media Sa</publisher><subject>Aged ; Aged, 80 and over ; Biomarkers ; Carcinoma, Non-Small-Cell Lung - diagnosis ; Carcinoma, Non-Small-Cell Lung - genetics ; Carcinoma, Non-Small-Cell Lung - mortality ; Carcinoma, Non-Small-Cell Lung - radiotherapy ; disease progression ; Female ; Gene Expression Profiling ; High-Throughput Nucleotide Sequencing ; Humans ; Immunology ; Life Sciences & Biomedicine ; Lung Neoplasms - diagnosis ; Lung Neoplasms - genetics ; Lung Neoplasms - mortality ; Lung Neoplasms - radiotherapy ; Male ; Middle Aged ; Neoplasm Staging ; non-small-cell lung cancer ; Positron Emission Tomography Computed Tomography ; Prognosis ; Radiosurgery ; Receptors, Antigen, T-Cell - genetics ; Receptors, Antigen, T-Cell - metabolism ; ROC Curve ; Science & Technology ; stereotactic body radiation therapy ; T-cell receptor sequencing ; Tomography, X-Ray Computed ; treatment failure ; V(D)J Recombination</subject><ispartof>Frontiers in immunology, 2021-10, Vol.12, p.719285-719285, Article 719285</ispartof><rights>Copyright © 2021 Wu, Zhu, Rudqvist, Welsh, Lee, Liao, Xu, Jiang, Zhu, Pan, Li, Zhou, He, Yin and Feng.</rights><rights>Copyright © 2021 Wu, Zhu, Rudqvist, Welsh, Lee, Liao, Xu, Jiang, Zhu, Pan, Li, Zhou, He, Yin and Feng 2021 Wu, Zhu, Rudqvist, Welsh, Lee, Liao, Xu, Jiang, Zhu, Pan, Li, Zhou, He, Yin and Feng</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>true</woscitedreferencessubscribed><woscitedreferencescount>3</woscitedreferencescount><woscitedreferencesoriginalsourcerecordid>wos000715737000001</woscitedreferencesoriginalsourcerecordid><citedby>FETCH-LOGICAL-c465t-667bdc74a0d7ca8bfcf74c50c155c3803c154bf02b0810d03821d8ac03b2ccec3</citedby><cites>FETCH-LOGICAL-c465t-667bdc74a0d7ca8bfcf74c50c155c3803c154bf02b0810d03821d8ac03b2ccec3</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/PMC8559517/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8559517/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,865,886,2103,2115,27929,27930,39263,53796,53798</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34733273$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wu, Lirong</creatorcontrib><creatorcontrib>Zhu, Jun</creatorcontrib><creatorcontrib>Rudqvist, Nils-Petter</creatorcontrib><creatorcontrib>Welsh, James</creatorcontrib><creatorcontrib>Lee, Percy</creatorcontrib><creatorcontrib>Liao, Zhongxing</creatorcontrib><creatorcontrib>Xu, Ting</creatorcontrib><creatorcontrib>Jiang, Ming</creatorcontrib><creatorcontrib>Zhu, Xiangzhi</creatorcontrib><creatorcontrib>Pan, Xuan</creatorcontrib><creatorcontrib>Li, Pansong</creatorcontrib><creatorcontrib>Zhou, Zhipeng</creatorcontrib><creatorcontrib>He, Xia</creatorcontrib><creatorcontrib>Yin, Rong</creatorcontrib><creatorcontrib>Feng, Jifeng</creatorcontrib><title>T-Cell Receptor Profiling and Prognosis After Stereotactic Body Radiation Therapy For Stage I Non-Small-Cell Lung Cancer</title><title>Frontiers in immunology</title><addtitle>FRONT IMMUNOL</addtitle><addtitle>Front Immunol</addtitle><description>Radiotherapy is known to influence immune function, including T cell receptor (TCR) repertoire. We evaluated the TCR repertoire before and after stereotactic body radiotherapy (SBRT) for stage I non-small-cell lung cancer (NSCLC) and explored correlations between TCR indexes and distant failure after SBRT. TCR repertoires were analyzed in peripheral blood mononuclear cells (PBMCs) collected before and after SBRT from 19 patients. TCR combinational diversity in V and J genes was assessed with multiplex PCR of genomic DNA from PBMCs and tested for associations with clinical response. All patients received definitive SBRT to a biologically effective dose of >=100 Gy. The number of unique TCR clones was decreased after SBRT versus before, but clonality and the Shannon Entropy did not change. Four patients (21%) developed distant metastases after SBRT (median 7 months); those patients had lower Shannon Entropy in post-SBRT samples than patients without metastasis. Patients with a low change in Shannon Entropy from before to after SBRT [(post-SBRT Shannon Entropy minus baseline Shannon)/(baseline Shannon) * 100] had poorer metastasis-free survival than those with high change in Shannon Entropy (P<0.001). Frequencies in V/J gene fragment expression in the TCR beta chain were also different for patients with or without metastases (two V fragments in baseline samples and 2 J and 9 V fragments in post-treatment samples). This comprehensive analysis of immune status before and after SBRT showed that quantitative assessments of TCRs can help evaluate prognosis in early-stage NSCLC.</description><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Biomarkers</subject><subject>Carcinoma, Non-Small-Cell Lung - diagnosis</subject><subject>Carcinoma, Non-Small-Cell Lung - genetics</subject><subject>Carcinoma, Non-Small-Cell Lung - mortality</subject><subject>Carcinoma, Non-Small-Cell Lung - radiotherapy</subject><subject>disease progression</subject><subject>Female</subject><subject>Gene Expression Profiling</subject><subject>High-Throughput Nucleotide Sequencing</subject><subject>Humans</subject><subject>Immunology</subject><subject>Life Sciences & Biomedicine</subject><subject>Lung Neoplasms - diagnosis</subject><subject>Lung Neoplasms - genetics</subject><subject>Lung Neoplasms - mortality</subject><subject>Lung Neoplasms - radiotherapy</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Neoplasm Staging</subject><subject>non-small-cell lung cancer</subject><subject>Positron Emission Tomography Computed Tomography</subject><subject>Prognosis</subject><subject>Radiosurgery</subject><subject>Receptors, Antigen, T-Cell - genetics</subject><subject>Receptors, Antigen, T-Cell - metabolism</subject><subject>ROC Curve</subject><subject>Science & Technology</subject><subject>stereotactic body radiation therapy</subject><subject>T-cell receptor sequencing</subject><subject>Tomography, X-Ray Computed</subject><subject>treatment failure</subject><subject>V(D)J Recombination</subject><issn>1664-3224</issn><issn>1664-3224</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>HGBXW</sourceid><sourceid>EIF</sourceid><sourceid>DOA</sourceid><recordid>eNqNUstu1DAUjRCIVqUfwAZ5iYQy-BHHzgapRBRGGgFqh7Xl-DF1ldiDnQDz9ziTMmp3eGHfa59zru17iuI1gitCePPeumGYVhhitGKowZw-K85RXVclwbh6_ig-Ky5Tuod5VA0hhL4szkjFCMGMnBd_tmVr-h7cGGX2Y4jgewzW9c7vgPR6znY-JJfAlR1NBLd5MmGUanQKfAz6AG6kdnJ0wYPtnYlyfwDXYcbJnQFr8DX48naQfb9U2UxZt5VemfiqeGFln8zlw3pR_Lj-tG2_lJtvn9ft1aZUVU3Hsq5ZpxWrJNRMSd5ZZVmlKFSIUkU4JDmoOgtxBzmCGhKOkeZSQdJhpYwiF8V60dVB3ot9dIOMBxGkE8eNEHdCxvya3giiDbeG1zVvSC7edBgpVVfMNpoSbHTW-rBo7aduMFoZP0bZPxF9euLdndiFX4JT2lDEssDbB4EYfk4mjWJwSeWfkd6EKQlMG1JDnNEZihaoiiGlaOypDIJiNoA4GkDMBhCLATLnzeP7nRj_2p0BfAH8Nl2wSTmTW3GCZYcwRBlhs1cgat14bGwbJj9m6rv_p5K_z7nOmQ</recordid><startdate>20211018</startdate><enddate>20211018</enddate><creator>Wu, Lirong</creator><creator>Zhu, Jun</creator><creator>Rudqvist, Nils-Petter</creator><creator>Welsh, James</creator><creator>Lee, Percy</creator><creator>Liao, Zhongxing</creator><creator>Xu, Ting</creator><creator>Jiang, Ming</creator><creator>Zhu, Xiangzhi</creator><creator>Pan, Xuan</creator><creator>Li, Pansong</creator><creator>Zhou, Zhipeng</creator><creator>He, Xia</creator><creator>Yin, Rong</creator><creator>Feng, Jifeng</creator><general>Frontiers Media Sa</general><general>Frontiers Media S.A</general><scope>BLEPL</scope><scope>DTL</scope><scope>HGBXW</scope><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>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20211018</creationdate><title>T-Cell Receptor Profiling and Prognosis After Stereotactic Body Radiation Therapy For Stage I Non-Small-Cell Lung Cancer</title><author>Wu, Lirong ; Zhu, Jun ; Rudqvist, Nils-Petter ; Welsh, James ; Lee, Percy ; Liao, Zhongxing ; Xu, Ting ; Jiang, Ming ; Zhu, Xiangzhi ; Pan, Xuan ; Li, Pansong ; Zhou, Zhipeng ; He, Xia ; Yin, Rong ; Feng, Jifeng</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c465t-667bdc74a0d7ca8bfcf74c50c155c3803c154bf02b0810d03821d8ac03b2ccec3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Biomarkers</topic><topic>Carcinoma, Non-Small-Cell Lung - diagnosis</topic><topic>Carcinoma, Non-Small-Cell Lung - genetics</topic><topic>Carcinoma, Non-Small-Cell Lung - mortality</topic><topic>Carcinoma, Non-Small-Cell Lung - radiotherapy</topic><topic>disease progression</topic><topic>Female</topic><topic>Gene Expression Profiling</topic><topic>High-Throughput Nucleotide Sequencing</topic><topic>Humans</topic><topic>Immunology</topic><topic>Life Sciences & Biomedicine</topic><topic>Lung Neoplasms - diagnosis</topic><topic>Lung Neoplasms - genetics</topic><topic>Lung Neoplasms - mortality</topic><topic>Lung Neoplasms - radiotherapy</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Neoplasm Staging</topic><topic>non-small-cell lung cancer</topic><topic>Positron Emission Tomography Computed Tomography</topic><topic>Prognosis</topic><topic>Radiosurgery</topic><topic>Receptors, Antigen, T-Cell - genetics</topic><topic>Receptors, Antigen, T-Cell - metabolism</topic><topic>ROC Curve</topic><topic>Science & Technology</topic><topic>stereotactic body radiation therapy</topic><topic>T-cell receptor sequencing</topic><topic>Tomography, X-Ray Computed</topic><topic>treatment failure</topic><topic>V(D)J Recombination</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wu, Lirong</creatorcontrib><creatorcontrib>Zhu, Jun</creatorcontrib><creatorcontrib>Rudqvist, Nils-Petter</creatorcontrib><creatorcontrib>Welsh, James</creatorcontrib><creatorcontrib>Lee, Percy</creatorcontrib><creatorcontrib>Liao, Zhongxing</creatorcontrib><creatorcontrib>Xu, Ting</creatorcontrib><creatorcontrib>Jiang, Ming</creatorcontrib><creatorcontrib>Zhu, Xiangzhi</creatorcontrib><creatorcontrib>Pan, Xuan</creatorcontrib><creatorcontrib>Li, Pansong</creatorcontrib><creatorcontrib>Zhou, Zhipeng</creatorcontrib><creatorcontrib>He, Xia</creatorcontrib><creatorcontrib>Yin, Rong</creatorcontrib><creatorcontrib>Feng, Jifeng</creatorcontrib><collection>Web of Science Core Collection</collection><collection>Science Citation Index Expanded</collection><collection>Web of Science - Science Citation Index Expanded - 2021</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Frontiers in immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wu, Lirong</au><au>Zhu, Jun</au><au>Rudqvist, Nils-Petter</au><au>Welsh, James</au><au>Lee, Percy</au><au>Liao, Zhongxing</au><au>Xu, Ting</au><au>Jiang, Ming</au><au>Zhu, Xiangzhi</au><au>Pan, Xuan</au><au>Li, Pansong</au><au>Zhou, Zhipeng</au><au>He, Xia</au><au>Yin, Rong</au><au>Feng, Jifeng</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>T-Cell Receptor Profiling and Prognosis After Stereotactic Body Radiation Therapy For Stage I Non-Small-Cell Lung Cancer</atitle><jtitle>Frontiers in immunology</jtitle><stitle>FRONT IMMUNOL</stitle><addtitle>Front Immunol</addtitle><date>2021-10-18</date><risdate>2021</risdate><volume>12</volume><spage>719285</spage><epage>719285</epage><pages>719285-719285</pages><artnum>719285</artnum><issn>1664-3224</issn><eissn>1664-3224</eissn><abstract>Radiotherapy is known to influence immune function, including T cell receptor (TCR) repertoire. We evaluated the TCR repertoire before and after stereotactic body radiotherapy (SBRT) for stage I non-small-cell lung cancer (NSCLC) and explored correlations between TCR indexes and distant failure after SBRT. TCR repertoires were analyzed in peripheral blood mononuclear cells (PBMCs) collected before and after SBRT from 19 patients. TCR combinational diversity in V and J genes was assessed with multiplex PCR of genomic DNA from PBMCs and tested for associations with clinical response. All patients received definitive SBRT to a biologically effective dose of >=100 Gy. The number of unique TCR clones was decreased after SBRT versus before, but clonality and the Shannon Entropy did not change. Four patients (21%) developed distant metastases after SBRT (median 7 months); those patients had lower Shannon Entropy in post-SBRT samples than patients without metastasis. Patients with a low change in Shannon Entropy from before to after SBRT [(post-SBRT Shannon Entropy minus baseline Shannon)/(baseline Shannon) * 100] had poorer metastasis-free survival than those with high change in Shannon Entropy (P<0.001). Frequencies in V/J gene fragment expression in the TCR beta chain were also different for patients with or without metastases (two V fragments in baseline samples and 2 J and 9 V fragments in post-treatment samples). This comprehensive analysis of immune status before and after SBRT showed that quantitative assessments of TCRs can help evaluate prognosis in early-stage NSCLC.</abstract><cop>LAUSANNE</cop><pub>Frontiers Media Sa</pub><pmid>34733273</pmid><doi>10.3389/fimmu.2021.719285</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Aged Aged, 80 and over Biomarkers Carcinoma, Non-Small-Cell Lung - diagnosis Carcinoma, Non-Small-Cell Lung - genetics Carcinoma, Non-Small-Cell Lung - mortality Carcinoma, Non-Small-Cell Lung - radiotherapy disease progression Female Gene Expression Profiling High-Throughput Nucleotide Sequencing Humans Immunology Life Sciences & Biomedicine Lung Neoplasms - diagnosis Lung Neoplasms - genetics Lung Neoplasms - mortality Lung Neoplasms - radiotherapy Male Middle Aged Neoplasm Staging non-small-cell lung cancer Positron Emission Tomography Computed Tomography Prognosis Radiosurgery Receptors, Antigen, T-Cell - genetics Receptors, Antigen, T-Cell - metabolism ROC Curve Science & Technology stereotactic body radiation therapy T-cell receptor sequencing Tomography, X-Ray Computed treatment failure V(D)J Recombination |
| title | T-Cell Receptor Profiling and Prognosis After Stereotactic Body Radiation Therapy For Stage I Non-Small-Cell Lung Cancer |
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