Giulia Becherucci, Cesare Ruffolo, Melania Scarpa, Federico Scognamiglio, Astghik Stepanyan, Isacco Maretto, Andromachi Kotsafti, Ottavia De Simoni, Pierluigi Pilati, Boris Franzato, Antonio Scapinello, Francesca Bergamo, Marco Massani, Tommaso Stecca, Anna Pozza, Ivana Cataldo, Stefano Brignola, Valerio Pellegrini, Matteo Fassan, Vincenza Guzzardo, Luca Dal Santo, Roberta Salmaso, Ceccon Carlotta, Angelo Paolo Dei Tos, Imerio Angriman, Gaya Spolverato, Valentina Chiminazzo, Silvia Negro, Chiara Vignotto, Francesco Marchegiani, Luca Facci, Giorgio Rivella, Quoc Riccardo Bao, Andrea Baldo, Salvatore Pucciarelli, Maurizio Zizzo, Gianluca Businello, Beatrice Salmaso, Dario Parini, Giovanni Pirozzolo, Alfonso Recordare, Giovanni Tagliente, Giovanni Bordignon, Roberto Merenda, Laurino Licia, Giulia Pozza, Mario Godina, Isabella Mondi, Daunia Verdi, Corrado Da Lio, Silvio Guerriero, Alessandra Piccioli, Giuseppe Portale, Matteo Zuin, Chiara Cipollari, Giulia Noaro, Roberto Cola, Salvatore Candioli, Laura Gavagna, Fabio Ricagna, Monica Ortenzi, Mario Guerrieri, Monica Tomassi, Umberto Tedeschi, Laura Marinelli, Mattia Barbareschi, Giovanni Bertalot, Alberto Brolese, Lavinia Ceccarini, Michele Antoniutti, Andrea Porzionato, Marco Agostini, Francesco Cavallin, Gaia Tussardi, Barbara Di Camillo, Romeo Bardini, Ignazio Castagliuolo, Marco Scarpa
{"title":"IMMUNOREACT 8：经肛门切除术治疗临床 N0 直肠癌患者局部肿瘤扩散的免疫标记物。","authors":"Giulia Becherucci, Cesare Ruffolo, Melania Scarpa, Federico Scognamiglio, Astghik Stepanyan, Isacco Maretto, Andromachi Kotsafti, Ottavia De Simoni, Pierluigi Pilati, Boris Franzato, Antonio Scapinello, Francesca Bergamo, Marco Massani, Tommaso Stecca, Anna Pozza, Ivana Cataldo, Stefano Brignola, Valerio Pellegrini, Matteo Fassan, Vincenza Guzzardo, Luca Dal Santo, Roberta Salmaso, Ceccon Carlotta, Angelo Paolo Dei Tos, Imerio Angriman, Gaya Spolverato, Valentina Chiminazzo, Silvia Negro, Chiara Vignotto, Francesco Marchegiani, Luca Facci, Giorgio Rivella, Quoc Riccardo Bao, Andrea Baldo, Salvatore Pucciarelli, Maurizio Zizzo, Gianluca Businello, Beatrice Salmaso, Dario Parini, Giovanni Pirozzolo, Alfonso Recordare, Giovanni Tagliente, Giovanni Bordignon, Roberto Merenda, Laurino Licia, Giulia Pozza, Mario Godina, Isabella Mondi, Daunia Verdi, Corrado Da Lio, Silvio Guerriero, Alessandra Piccioli, Giuseppe Portale, Matteo Zuin, Chiara Cipollari, Giulia Noaro, Roberto Cola, Salvatore Candioli, Laura Gavagna, Fabio Ricagna, Monica Ortenzi, Mario Guerrieri, Monica Tomassi, Umberto Tedeschi, Laura Marinelli, Mattia Barbareschi, Giovanni Bertalot, Alberto Brolese, Lavinia Ceccarini, Michele Antoniutti, Andrea Porzionato, Marco Agostini, Francesco Cavallin, Gaia Tussardi, Barbara Di Camillo, Romeo Bardini, Ignazio Castagliuolo, Marco Scarpa","doi":"10.1016/j.surg.2024.09.043","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Transanal excision of rectal cancer can be considered the definitive surgical treatment if the depth spread is T1 or lower, and the lesion is completely included within the resection margin. This study aims to analyze the immune microenvironment in healthy rectal mucosa as a possible predictor of tumor infiltration depth, lateral tumor spread, and recurrence of rectal cancer after transanal local excision.</p><p><strong>Methods: </strong>This study is a subanalysis of data from the IMMUNOREACT 1 and 2 trials (NCT04915326 and NCT04917263, respectively) including all the patients who underwent transanal excision of rectal cancer. This multicentric study collected healthy mucosa surrounding the neoplasms of patients with rectal cancer. A panel of immune markers was investigated at immunohistochemistry: CD3, CD4, CD8, CD8β, Tbet, FoxP3, PD-L1, MSH6, and PMS2 and CD80. Flow cytometry determined the proportion of epithelial cells expressing CD80, CD86, CD40, HLA ABC or HLA DR and the proportion of activated CD8+ T cells, CD4+ Th1 cells, and Treg.</p><p><strong>Results: </strong>Receiver operating characteristic curve analysis for predicting deep tumor spread showed an area under the curve of 0.70 (95% confidence interval: 0.60-0.80) for CD25+FoxP3+ cell rate and 0.74 (95% confidence interval: 0.53-0.92) for CK+CD86+ cell rate. Receiver operating characteristic curve analysis for predicting lateral tumor spread showed an area under the curve of 0.82 (95% confidence interval: 0.61-0.99) for CD8+CD38+ MFI, 0.96 (95% confidence interval: 0.85-0.99) for CD8β infiltration, and 0.97 (95% confidence interval: 0.87-0.99) for CK+HLAabc+ cell rate. Receiver operating characteristic curve analysis for predicting recurrence showed an area under the curve of 0.93 (95% confidence interval: 0.76-0.99) for CD8+CD38+ MFI and 0.94 (95% confidence interval: 0.78-0.99) for CD8+CD28+ MFI. Low CD8+CD38+ MFI and low CD8+CD28+ MFI were associated with shorter disease-free survival (P = .025 and P = .021, respectively).</p><p><strong>Conclusion: </strong>Our study showed that the association between the high proportion of epithelial cells acting as presenting cells and deep or lateral tumor spread may be explained by the presence of a greater tumor load at the site. Moreover, it showed that weak activation of CD8+ T cells within the rectal mucosa is associated with lateral tumor spread and eventually a higher recurrence rate. The mucosal level of CD8β infiltration detected at immunohistochemistry might be tested as a marker of lateral tumor spread and potentially translated into clinical practice.</p>","PeriodicalId":22152,"journal":{"name":"Surgery","volume":" ","pages":"108902"},"PeriodicalIF":3.2000,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"IMMUNOREACT 8: Immune markers of local tumor spread in patients undergoing transanal excision for clinically N0 rectal cancer.\",\"authors\":\"Giulia Becherucci, Cesare Ruffolo, Melania Scarpa, Federico Scognamiglio, Astghik Stepanyan, Isacco Maretto, Andromachi Kotsafti, Ottavia De Simoni, Pierluigi Pilati, Boris Franzato, Antonio Scapinello, Francesca Bergamo, Marco Massani, Tommaso Stecca, Anna Pozza, Ivana Cataldo, Stefano Brignola, Valerio Pellegrini, Matteo Fassan, Vincenza Guzzardo, Luca Dal Santo, Roberta Salmaso, Ceccon Carlotta, Angelo Paolo Dei Tos, Imerio Angriman, Gaya Spolverato, Valentina Chiminazzo, Silvia Negro, Chiara Vignotto, Francesco Marchegiani, Luca Facci, Giorgio Rivella, Quoc Riccardo Bao, Andrea Baldo, Salvatore Pucciarelli, Maurizio Zizzo, Gianluca Businello, Beatrice Salmaso, Dario Parini, Giovanni Pirozzolo, Alfonso Recordare, Giovanni Tagliente, Giovanni Bordignon, Roberto Merenda, Laurino Licia, Giulia Pozza, Mario Godina, Isabella Mondi, Daunia Verdi, Corrado Da Lio, Silvio Guerriero, Alessandra Piccioli, Giuseppe Portale, Matteo Zuin, Chiara Cipollari, Giulia Noaro, Roberto Cola, Salvatore Candioli, Laura Gavagna, Fabio Ricagna, Monica Ortenzi, Mario Guerrieri, Monica Tomassi, Umberto Tedeschi, Laura Marinelli, Mattia Barbareschi, Giovanni Bertalot, Alberto Brolese, Lavinia Ceccarini, Michele Antoniutti, Andrea Porzionato, Marco Agostini, Francesco Cavallin, Gaia Tussardi, Barbara Di Camillo, Romeo Bardini, Ignazio Castagliuolo, Marco Scarpa\",\"doi\":\"10.1016/j.surg.2024.09.043\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Transanal excision of rectal cancer can be considered the definitive surgical treatment if the depth spread is T1 or lower, and the lesion is completely included within the resection margin. This study aims to analyze the immune microenvironment in healthy rectal mucosa as a possible predictor of tumor infiltration depth, lateral tumor spread, and recurrence of rectal cancer after transanal local excision.</p><p><strong>Methods: </strong>This study is a subanalysis of data from the IMMUNOREACT 1 and 2 trials (NCT04915326 and NCT04917263, respectively) including all the patients who underwent transanal excision of rectal cancer. This multicentric study collected healthy mucosa surrounding the neoplasms of patients with rectal cancer. A panel of immune markers was investigated at immunohistochemistry: CD3, CD4, CD8, CD8β, Tbet, FoxP3, PD-L1, MSH6, and PMS2 and CD80. Flow cytometry determined the proportion of epithelial cells expressing CD80, CD86, CD40, HLA ABC or HLA DR and the proportion of activated CD8+ T cells, CD4+ Th1 cells, and Treg.</p><p><strong>Results: </strong>Receiver operating characteristic curve analysis for predicting deep tumor spread showed an area under the curve of 0.70 (95% confidence interval: 0.60-0.80) for CD25+FoxP3+ cell rate and 0.74 (95% confidence interval: 0.53-0.92) for CK+CD86+ cell rate. Receiver operating characteristic curve analysis for predicting lateral tumor spread showed an area under the curve of 0.82 (95% confidence interval: 0.61-0.99) for CD8+CD38+ MFI, 0.96 (95% confidence interval: 0.85-0.99) for CD8β infiltration, and 0.97 (95% confidence interval: 0.87-0.99) for CK+HLAabc+ cell rate. Receiver operating characteristic curve analysis for predicting recurrence showed an area under the curve of 0.93 (95% confidence interval: 0.76-0.99) for CD8+CD38+ MFI and 0.94 (95% confidence interval: 0.78-0.99) for CD8+CD28+ MFI. Low CD8+CD38+ MFI and low CD8+CD28+ MFI were associated with shorter disease-free survival (P = .025 and P = .021, respectively).</p><p><strong>Conclusion: </strong>Our study showed that the association between the high proportion of epithelial cells acting as presenting cells and deep or lateral tumor spread may be explained by the presence of a greater tumor load at the site. Moreover, it showed that weak activation of CD8+ T cells within the rectal mucosa is associated with lateral tumor spread and eventually a higher recurrence rate. The mucosal level of CD8β infiltration detected at immunohistochemistry might be tested as a marker of lateral tumor spread and potentially translated into clinical practice.</p>\",\"PeriodicalId\":22152,\"journal\":{\"name\":\"Surgery\",\"volume\":\" \",\"pages\":\"108902\"},\"PeriodicalIF\":3.2000,\"publicationDate\":\"2025-02-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Surgery\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.surg.2024.09.043\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/11/20 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"SURGERY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Surgery","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.surg.2024.09.043","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/11/20 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"SURGERY","Score":null,"Total":0}
IMMUNOREACT 8: Immune markers of local tumor spread in patients undergoing transanal excision for clinically N0 rectal cancer.
Background: Transanal excision of rectal cancer can be considered the definitive surgical treatment if the depth spread is T1 or lower, and the lesion is completely included within the resection margin. This study aims to analyze the immune microenvironment in healthy rectal mucosa as a possible predictor of tumor infiltration depth, lateral tumor spread, and recurrence of rectal cancer after transanal local excision.
Methods: This study is a subanalysis of data from the IMMUNOREACT 1 and 2 trials (NCT04915326 and NCT04917263, respectively) including all the patients who underwent transanal excision of rectal cancer. This multicentric study collected healthy mucosa surrounding the neoplasms of patients with rectal cancer. A panel of immune markers was investigated at immunohistochemistry: CD3, CD4, CD8, CD8β, Tbet, FoxP3, PD-L1, MSH6, and PMS2 and CD80. Flow cytometry determined the proportion of epithelial cells expressing CD80, CD86, CD40, HLA ABC or HLA DR and the proportion of activated CD8+ T cells, CD4+ Th1 cells, and Treg.
Results: Receiver operating characteristic curve analysis for predicting deep tumor spread showed an area under the curve of 0.70 (95% confidence interval: 0.60-0.80) for CD25+FoxP3+ cell rate and 0.74 (95% confidence interval: 0.53-0.92) for CK+CD86+ cell rate. Receiver operating characteristic curve analysis for predicting lateral tumor spread showed an area under the curve of 0.82 (95% confidence interval: 0.61-0.99) for CD8+CD38+ MFI, 0.96 (95% confidence interval: 0.85-0.99) for CD8β infiltration, and 0.97 (95% confidence interval: 0.87-0.99) for CK+HLAabc+ cell rate. Receiver operating characteristic curve analysis for predicting recurrence showed an area under the curve of 0.93 (95% confidence interval: 0.76-0.99) for CD8+CD38+ MFI and 0.94 (95% confidence interval: 0.78-0.99) for CD8+CD28+ MFI. Low CD8+CD38+ MFI and low CD8+CD28+ MFI were associated with shorter disease-free survival (P = .025 and P = .021, respectively).
Conclusion: Our study showed that the association between the high proportion of epithelial cells acting as presenting cells and deep or lateral tumor spread may be explained by the presence of a greater tumor load at the site. Moreover, it showed that weak activation of CD8+ T cells within the rectal mucosa is associated with lateral tumor spread and eventually a higher recurrence rate. The mucosal level of CD8β infiltration detected at immunohistochemistry might be tested as a marker of lateral tumor spread and potentially translated into clinical practice.
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For 66 years, Surgery has published practical, authoritative information about procedures, clinical advances, and major trends shaping general surgery. Each issue features original scientific contributions and clinical reports. Peer-reviewed articles cover topics in oncology, trauma, gastrointestinal, vascular, and transplantation surgery. The journal also publishes papers from the meetings of its sponsoring societies, the Society of University Surgeons, the Central Surgical Association, and the American Association of Endocrine Surgeons.
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