Scientific Reports (Nov 2024)

IMMUNOREACT 9 metachronous rectal cancers have high HLA-ABC expression on healthy epithelium but a lower infiltration of CD3+ T cells than primary lesions

  • 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

DOI
https://doi.org/10.1038/s41598-024-80299-0
Journal volume & issue
Vol. 14, no. 1
pp. 1 – 11

Abstract

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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.