IMMUNOREACT 9 metachronous rectal cancers have high HLA-ABC expression on healthy epithelium but a lower infiltration of CD3+ T cells than primary lesions
Abstract Lynch syndrome is rarely associated with rectal cancer (RC) and thus, metachronous RC has been scarcely investigated. This study aimed to analyze the mucosal immune microenvironment in sporadic and metachronous RC. We analyzed the mucosal immune microenvironment in the 25 metachronous RCs p...
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2024-11-01
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| author | Beatrice Salmaso Melania Scarpa Valerio Pellegrini Astghik Stepanyan Roberta Salmaso Andromachi Kotsafti Federico Scognamiglio Dario Gregori Giorgio Rivella Ottavia De Simoni Giulia Becherucci Silvia Negro Chiara Vignotto Gaya Spolverato Cesare Ruffolo Imerio Angriman Francesca Bergamo Valentina Chiminazzo Isacco Maretto Maurizio Zizzo Francesco Marchegiani Luca Facci Stefano Brignola Gianluca Businello Laurino Licia Vincenza Guzzardo Luca Dal Santo Ceccon Carlotta Marco Massani Anna Pozza Ivana Cataldo Tommaso Stecca Angelo Paolo Dei Tos Vittorina Zagonel Pierluigi Pilati Boris Franzato Antonio Scapinello Giulia Pozza Mario Godina Giovanni Pirozzolo Alfonso Recordare Isabella Mondi Corrado Da Lio Roberto Merenda Giovanni Bordignon Daunia Verdi Luca Saadeh Silvio Guerriero Alessandra Piccioli Giulia Noaro Roberto Cola Giuseppe Portale Chiara Cipollari Matteo Zuin Salvatore Candioli Laura Gavagna Fabio Ricagna Monica Ortenzi Mario Guerrieri Giovanni Tagliente Monica Tomassi Umberto Tedeschi Andrea Porzionato Marco Agostini Riccardo Quoc Bao Francesco Cavallin Gaia Tussardi Barbara Di Camillo Romeo Bardini Ignazio Castagliuolo Salvatore Pucciarelli Matteo Fassan Marco Scarpa |
| author_facet | Beatrice Salmaso Melania Scarpa Valerio Pellegrini Astghik Stepanyan Roberta Salmaso Andromachi Kotsafti Federico Scognamiglio Dario Gregori Giorgio Rivella Ottavia De Simoni Giulia Becherucci Silvia Negro Chiara Vignotto Gaya Spolverato Cesare Ruffolo Imerio Angriman Francesca Bergamo Valentina Chiminazzo Isacco Maretto Maurizio Zizzo Francesco Marchegiani Luca Facci Stefano Brignola Gianluca Businello Laurino Licia Vincenza Guzzardo Luca Dal Santo Ceccon Carlotta Marco Massani Anna Pozza Ivana Cataldo Tommaso Stecca Angelo Paolo Dei Tos Vittorina Zagonel Pierluigi Pilati Boris Franzato Antonio Scapinello Giulia Pozza Mario Godina Giovanni Pirozzolo Alfonso Recordare Isabella Mondi Corrado Da Lio Roberto Merenda Giovanni Bordignon Daunia Verdi Luca Saadeh Silvio Guerriero Alessandra Piccioli Giulia Noaro Roberto Cola Giuseppe Portale Chiara Cipollari Matteo Zuin Salvatore Candioli Laura Gavagna Fabio Ricagna Monica Ortenzi Mario Guerrieri Giovanni Tagliente Monica Tomassi Umberto Tedeschi Andrea Porzionato Marco Agostini Riccardo Quoc Bao Francesco Cavallin Gaia Tussardi Barbara Di Camillo Romeo Bardini Ignazio Castagliuolo Salvatore Pucciarelli Matteo Fassan Marco Scarpa |
| author_sort | Beatrice Salmaso |
| collection | DOAJ |
| description | Abstract Lynch syndrome is rarely associated with rectal cancer (RC) and thus, metachronous RC has been scarcely investigated. This study aimed to analyze the mucosal immune microenvironment in sporadic and metachronous RC. We analyzed the mucosal immune microenvironment in the 25 metachronous RCs present in the IMMUNOREACT 1 and 2 multicentre observational studies (624 patients). A panel of immune markers was retrospectively investigated at immunohistochemistry: CD3, CD4, CD8, CD8b, Tbet, FoxP3, PD-L1, MSH6, and PMS2 and CD80. Single-cell suspensions were subjected to flow-cytometry to determine the proportion of epithelial cells (pan-cytokeratin) acting as antigen-presenting cells (expressing CD80, CD86, HLA-ABC) and the proportion of activated CD8 + T cells (CD8 + positive for CD28, CD38), inhibitory T cells (CD3 + CTLA-4+) of activated CD4 + T helper cells (CD4 + CD25+) and activated T regulatory cells (CD4 + CD25 + FoxP3+). No mismatch repair gene deficiencies were observed in the patients. The previous history of colorectal adenoma was significantly more frequent in metachronous RC. In healthy epithelial cells, HLA-ABC expression was significantly higher in patients with metachronous RC. In therapy-naïve metachronous RC patients, a significantly lower level of circulating lymphocytes and CD3 + T-cell infiltration in the healthy mucosa surrounding the RC was observed compared to patients with non-metachronous cancer. Our study supports the hypothesis that metachronous RC can occur in a cancerization field in patients with weak systemic and local immune systems. The peculiar site of RC makes the mismatch-repair genes deficiency in metachronous cancer onset less relevant. |
| format | Article |
| id | doaj-art-cda4fa0daa04498d819fda0dd2dd459b |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-cda4fa0daa04498d819fda0dd2dd459b2024-12-01T12:18:28ZengNature PortfolioScientific Reports2045-23222024-11-0114111110.1038/s41598-024-80299-0IMMUNOREACT 9 metachronous rectal cancers have high HLA-ABC expression on healthy epithelium but a lower infiltration of CD3+ T cells than primary lesionsBeatrice Salmaso0Melania Scarpa1Valerio Pellegrini2Astghik Stepanyan3Roberta Salmaso4Andromachi Kotsafti5Federico Scognamiglio6Dario Gregori7Giorgio Rivella8Ottavia De Simoni9Giulia Becherucci10Silvia Negro11Chiara Vignotto12Gaya Spolverato13Cesare Ruffolo14Imerio Angriman15Francesca Bergamo16Valentina Chiminazzo17Isacco Maretto18Maurizio Zizzo19Francesco Marchegiani20Luca Facci21Stefano Brignola22Gianluca Businello23Laurino Licia24Vincenza Guzzardo25Luca Dal Santo26Ceccon Carlotta27Marco Massani28Anna Pozza29Ivana Cataldo30Tommaso Stecca31Angelo Paolo Dei Tos32Vittorina Zagonel33Pierluigi Pilati34Boris Franzato35Antonio Scapinello36Giulia Pozza37Mario Godina38Giovanni Pirozzolo39Alfonso Recordare40Isabella Mondi41Corrado Da Lio42Roberto Merenda43Giovanni Bordignon44Daunia Verdi45Luca Saadeh46Silvio Guerriero47Alessandra Piccioli48Giulia Noaro49Roberto Cola50Giuseppe Portale51Chiara Cipollari52Matteo Zuin53Salvatore Candioli54Laura Gavagna55Fabio Ricagna56Monica Ortenzi57Mario Guerrieri58Giovanni Tagliente59Monica Tomassi60Umberto Tedeschi61Andrea Porzionato62Marco Agostini63Riccardo Quoc Bao64Francesco Cavallin65Gaia Tussardi66Barbara Di Camillo67Romeo Bardini68Ignazio Castagliuolo69Salvatore Pucciarelli70Matteo Fassan71Marco Scarpa72Azienda ULSS 5 PolesanaVeneto Institute of Oncology IOV-IRCCSAzienda ULSS 2 Marca TrevigianaAzienda Ospedale Università di PadovaAzienda Ospedale Università di PadovaVeneto Institute of Oncology IOV-IRCCSAzienda Ospedale Università di PadovaAzienda Ospedale Università di PadovaAzienda Ospedale Università di PadovaVeneto Institute of Oncology IOV-IRCCSAzienda Ospedale Università di PadovaAzienda Ospedale Università di PadovaAzienda Ospedale Università di PadovaAzienda Ospedale Università di PadovaAzienda Ospedale Università di PadovaAzienda Ospedale Università di PadovaVeneto Institute of Oncology IOV-IRCCSAzienda Ospedale Università di PadovaAzienda Ospedale Università di PadovaArcispedale Santa Maria Nuova IRCCS, SurgeryAzienda Ospedale Università di PadovaAzienda Ospedale Università di PadovaAzienda ULSS 2 Marca TrevigianaAzienda ULSS 5 PolesanaAzienda ULSS 3 SerenissimaAzienda Ospedale Università di PadovaAzienda Ospedale Università di PadovaAzienda ULSS 2 Marca TrevigianaAzienda ULSS 2 Marca TrevigianaAzienda ULSS 2 Marca TrevigianaAzienda ULSS 2 Marca TrevigianaAzienda ULSS 2 Marca TrevigianaAzienda Ospedale Università di PadovaVeneto Institute of Oncology IOV-IRCCSVeneto Institute of Oncology IOV-IRCCSVeneto Institute of Oncology IOV-IRCCSVeneto Institute of Oncology IOV-IRCCSAzienda Ospedale Università di PadovaAzienda ULSS 3 SerenissimaAzienda ULSS 3 SerenissimaAzienda ULSS 3 SerenissimaAzienda ULSS 3 SerenissimaAzienda ULSS 3 SerenissimaAzienda ULSS 3 SerenissimaAzienda ULSS 3 SerenissimaAzienda ULSS 3 SerenissimaAzienda Ospedale Università di PadovaOspedale di Fermo, ASUR 4Ospedale di Fermo, ASUR 4Azienda ULSS 6 EuganeaAzienda ULSS 6 EuganeaAzienda ULSS 6 EuganeaAzienda ULSS 6 EuganeaAzienda ULSS 6 EuganeaAzienda ULSS 1 DolomitiAzienda ULSS 1 DolomitiAzienda ULSS 1 DolomitiAzienda Ospedaliero Universitaria Ospedali Riuniti di AnconaAzienda Ospedaliero Universitaria Ospedali Riuniti di AnconaAzienda ULSS 3 SerenissimaPoliclinico di AbanoPoliclinico di AbanoAzienda Ospedale Università di PadovaAzienda Ospedale Università di PadovaAzienda Ospedale Università di PadovaIndependent StatisticianAzienda Ospedale Università di PadovaDepartment of Information Engineering DEI, University of PaduaAzienda Ospedale Università di PadovaAzienda Ospedale Università di PadovaAzienda Ospedale Università di PadovaVeneto Institute of Oncology IOV-IRCCSAzienda Ospedale Università di PadovaAbstract Lynch syndrome is rarely associated with rectal cancer (RC) and thus, metachronous RC has been scarcely investigated. This study aimed to analyze the mucosal immune microenvironment in sporadic and metachronous RC. We analyzed the mucosal immune microenvironment in the 25 metachronous RCs present in the IMMUNOREACT 1 and 2 multicentre observational studies (624 patients). A panel of immune markers was retrospectively investigated at immunohistochemistry: CD3, CD4, CD8, CD8b, Tbet, FoxP3, PD-L1, MSH6, and PMS2 and CD80. Single-cell suspensions were subjected to flow-cytometry to determine the proportion of epithelial cells (pan-cytokeratin) acting as antigen-presenting cells (expressing CD80, CD86, HLA-ABC) and the proportion of activated CD8 + T cells (CD8 + positive for CD28, CD38), inhibitory T cells (CD3 + CTLA-4+) of activated CD4 + T helper cells (CD4 + CD25+) and activated T regulatory cells (CD4 + CD25 + FoxP3+). No mismatch repair gene deficiencies were observed in the patients. The previous history of colorectal adenoma was significantly more frequent in metachronous RC. In healthy epithelial cells, HLA-ABC expression was significantly higher in patients with metachronous RC. In therapy-naïve metachronous RC patients, a significantly lower level of circulating lymphocytes and CD3 + T-cell infiltration in the healthy mucosa surrounding the RC was observed compared to patients with non-metachronous cancer. Our study supports the hypothesis that metachronous RC can occur in a cancerization field in patients with weak systemic and local immune systems. The peculiar site of RC makes the mismatch-repair genes deficiency in metachronous cancer onset less relevant.https://doi.org/10.1038/s41598-024-80299-0 |
| spellingShingle | Beatrice Salmaso Melania Scarpa Valerio Pellegrini Astghik Stepanyan Roberta Salmaso Andromachi Kotsafti Federico Scognamiglio Dario Gregori Giorgio Rivella Ottavia De Simoni Giulia Becherucci Silvia Negro Chiara Vignotto Gaya Spolverato Cesare Ruffolo Imerio Angriman Francesca Bergamo Valentina Chiminazzo Isacco Maretto Maurizio Zizzo Francesco Marchegiani Luca Facci Stefano Brignola Gianluca Businello Laurino Licia Vincenza Guzzardo Luca Dal Santo Ceccon Carlotta Marco Massani Anna Pozza Ivana Cataldo Tommaso Stecca Angelo Paolo Dei Tos Vittorina Zagonel Pierluigi Pilati Boris Franzato Antonio Scapinello Giulia Pozza Mario Godina Giovanni Pirozzolo Alfonso Recordare Isabella Mondi Corrado Da Lio Roberto Merenda Giovanni Bordignon Daunia Verdi Luca Saadeh Silvio Guerriero Alessandra Piccioli Giulia Noaro Roberto Cola Giuseppe Portale Chiara Cipollari Matteo Zuin Salvatore Candioli Laura Gavagna Fabio Ricagna Monica Ortenzi Mario Guerrieri Giovanni Tagliente Monica Tomassi Umberto Tedeschi Andrea Porzionato Marco Agostini Riccardo Quoc Bao Francesco Cavallin Gaia Tussardi Barbara Di Camillo Romeo Bardini Ignazio Castagliuolo Salvatore Pucciarelli Matteo Fassan Marco Scarpa IMMUNOREACT 9 metachronous rectal cancers have high HLA-ABC expression on healthy epithelium but a lower infiltration of CD3+ T cells than primary lesions Scientific Reports |
| title | IMMUNOREACT 9 metachronous rectal cancers have high HLA-ABC expression on healthy epithelium but a lower infiltration of CD3+ T cells than primary lesions |
| title_full | IMMUNOREACT 9 metachronous rectal cancers have high HLA-ABC expression on healthy epithelium but a lower infiltration of CD3+ T cells than primary lesions |
| title_fullStr | IMMUNOREACT 9 metachronous rectal cancers have high HLA-ABC expression on healthy epithelium but a lower infiltration of CD3+ T cells than primary lesions |
| title_full_unstemmed | IMMUNOREACT 9 metachronous rectal cancers have high HLA-ABC expression on healthy epithelium but a lower infiltration of CD3+ T cells than primary lesions |
| title_short | IMMUNOREACT 9 metachronous rectal cancers have high HLA-ABC expression on healthy epithelium but a lower infiltration of CD3+ T cells than primary lesions |
| title_sort | immunoreact 9 metachronous rectal cancers have high hla abc expression on healthy epithelium but a lower infiltration of cd3 t cells than primary lesions |
| url | https://doi.org/10.1038/s41598-024-80299-0 |
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