IMMUNOREACT 4: Peritumoral Microenvironment Associated with Anastomotic Leaks After Surgery for Rectal Cancer
| Title: | IMMUNOREACT 4: Peritumoral Microenvironment Associated with Anastomotic Leaks After Surgery for Rectal Cancer |
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| Authors: | Ottavia De Simoni; Melania Scarpa; Francesco Cavallin; Andromachi Kotsafti; Francesco Marchegiani; Astghik Stepanyan; Gaia Tussardi; Antonio Rosato; Gaya Spolverato; Imerio Angriman; Emanuele Damiano Luca Urso; Cesare Ruffolo; Luca Maria Saadeh; Isacco Maretto; Quoc Riccardo Bao; Silvia Negro; Chiara Vignotto; Luca Facci; Giorgio Rivella; Antonella D’Angelo; Anna Matteazzi; Francesca Galuppini; Vincenza Guzzardo; Roberta Salmaso; Valerio Pellegrini; Stefano Brignola; Carlotta Ceccon; Tommaso Stecca; Anna Pozza; Marco Massani; Pierluigi Pilati; Mario Gruppo; Boris Franzato; Ivana Cataldo; Giuseppe Portale; Chiara Cipollari; Matteo Zuin; Licia Laurino; Luca Dal Santo; Giovanni Pirozzolo; Alfonso Recordare; Lavinia Ceccarini; Michele Antoniutti; Laura Marinelli; Alberto Brolese; Mattia Barbareschi; Giovanni Bertalot; Monica Ortenzi; Mario Guerrieri; Maurizio Zizzo; Lorenzo Dell’Atti; Silvio Guerriero; Alessandra Piccioli; Giulia Pozza; Mario Godina; Isabella Mondi; Daunia Verdi; Corrado Da Lio; Giulia Noaro; Roberto Cola; Giovanni Bordignon; Roberto Merenda; Giulia Becherucci; Laura Gavagna; Salvatore Candioli; Giovanni Tagliente; Umberto Tedeschi; Dario Parini; Beatrice Salmaso; Gianluca Businello; Loretta Di Cristoforo; Francesca Bergamo; Andrea Porzionato; Federico Scognamiglio; Romeo Bardini; Salvatore Pucciarelli; Marco Agostini; Valentina Chiminazzo; Dario Gregori; Barbara Di Camillo; Ignazio Castagliuolo; Angelo Paolo Dei Tos; Matteo Fassan; Marco Scarpa |
| Source: | Cancers ; Volume 18 ; Issue 4 ; Pages: 571 |
| Publisher Information: | Multidisciplinary Digital Publishing Institute |
| Publication Year: | 2026 |
| Collection: | MDPI Open Access Publishing |
| Subject Terms: | rectal cancer; anastomotic leak; immune surveillance markers |
| Description: | Background: Anastomotic leaks (ALs) remain a critical complication after rectal cancer surgery. Emerging evidence suggests that local immune dysregulation may play a key role in anastomotic healing. We investigated the immune microenvironment of histologically normal, tumor-adjacent rectal mucosa—a tumor-conditioned field—as a potential substrate for AL predisposition. Methods: IMMUNOREACT 4 is a sub-analysis of the IMMUNOREACT project (clinicaltrials.gov NCT04915326 and NCT04915326), a multicenter translational study evaluating immune features of histologically normal, tumor-adjacent rectal mucosa of patients undergoing colorectal anastomosis. A prospective cohort (n = 121) was analyzed using flow cytometry, in addition to a retrospective cohort (n = 262) using immunohistochemistry. Immune markers of epithelial activation and lymphocyte subsets were compared between patients with and without postoperative ALs. Exploratory predictive models combining immune and clinical variables were developed and evaluated using discrimination, calibration and decision curve analyses. Results: At flow cytometry, the CK+HLAabc+ MFI (AUC 0.66, 95% CI 0.52–0.80), CD8+CD38+ cell rate (AUC 0.65, 95% CI 0.52–0.78) and CD3+CTLA4+ cell rate (AUC 0.65, 95% CI 0.51–0.80) showed moderate predictive potential for ALs. In immunohistochemistry, CD3+ (AUC 0.57, 95% CI 0.54–0.60), CD8+ (AUC 0.57, 95% CI 0.52–0.62), CD8β+ (AUC 0.59, 95% CI 0.53–0.65) and Tbet+ (AUC 0.60, 95% CI 0.56–0.64) showed some predictive ability for ALs. The model including CD8β+, the BMI, neutrophile/lymphocyte ratio and tumor location had an AUC of 0.67 (95% CI 0.62–0.72). Conclusions: Immune activation within histologically normal, tumor-adjacent rectal mucosa—characterized by epithelial HLA upregulation and cytotoxic or Th1 T cell infiltration—is associated with postoperative ALs. Although predictive accuracy is limited, these findings support the concept that a tumor-conditioned immune microenvironment may predispose patients to impaired anastomotic healing. ... |
| Document Type: | text |
| File Description: | application/pdf |
| Language: | English |
| Relation: | Molecular Cancer Biology; https://dx.doi.org/10.3390/cancers18040571 |
| DOI: | 10.3390/cancers18040571 |
| Availability: | https://doi.org/10.3390/cancers18040571 |
| Rights: | https://creativecommons.org/licenses/by/4.0/ |
| Accession Number: | edsbas.45BA7442 |
| Database: | BASE |