IMMUNOREACT 9: METACHRONOUS RECTAL CANCER ARE FREQUENTLY FROM PREVIOUS RECTAL OR SIGMOID CANCER AND HAVE A LOW INFILTRATION OF CD8+ T CELLS
Beatrice Salmaso*1, Melania Scarpa2, Astghik Stepanyan1, Roberta Salmaso1, Andromachi Kotsafti2, Ottavia De Simoni2, Giulia Becherucci1, Silvia Negro1, Chiara Vignotto1, Gaya Spolverato1, Federico Scognamiglio1, Cesare Ruffolo1, Imerio Angriman1, Francesca Bergamo2, Valentina Chiminazzo1, Isacco Maretto1, Maurizio Zizzo3, Francesco Marchegiani1, Luca Facci1, Stefano Brignola4, Gianluca Businello5, Vincenza Guzzardo1, Luca Dal Santo1, Carlotta Ceccon1, Marco Massani4, Anna Pozza4, Ivana Cataldo4, Tommaso Stecca4, Angelo Dei Tos1, Vittorina Zagonel2, Pierluigi Pilati2, Boris Franzato2, Antonio Scapinello2, Giovanni Pirozzolo6, Andrea Porzionato2, Marco Agostini2, Quoc Riccardo Bao1, Francesco Cavallin1, Barbara Di Camillo7, Romeo Bardini1, Ignazio Castagliuolo1, Salvatore Pucciarelli1, Matteo Fassan1, Marco Scarpa1
1Chirurgia Generale 3, Azienda Ospedale Universita Padova, Padova, Veneto, Italy; 2Istituto Oncologico Veneto Istituto di Ricovero e Cura a Carattere Scientifico, Padova, Veneto, Italy; 3Arcispedale Santa Maria Nuova di Reggio Emilia, Reggio Emilia, Emilia-Romagna, Italy; 4Azienda ULSS n 2 Marca Trevigiana, Treviso, Veneto, Italy; 5Azienda ULSS 5 Polesana, Rovigo, Veneto, Italy; 6Azienda ULSS 3 Serenissima, Venezia, Veneto, Italy; 7Universita degli Studi di Padova Dipartimento di Ingegneria Industriale, Padova, Veneto, Italy
Background
In a previous study, we demonstrated that the frequency of mismatch repair genes defect was similar in metachronous and sporadic colorectal cancer while an altered immune microenvironment may be a crucial factor for the occurrence of metachronous ones. The density of tumor-infiltrating lymphocytes (TIL) is an independent predictor of outcome in patients with colorectal cancer, and our hypothesis is that they can be involved in the onset of metachronous rectal cancer. The aim of this study was to analyze the tumor microenvironment in sporadic and metachronous rectal cancer.
Methods
This study is a sub-analysis of data from the IMMUNOREACT 1 and 2 (NCT04915326 and NCT04917263) including all the patients whose records had information about the past medical history. We defined as metachronous cancer a rectal cancer arising after a previous colorectal cancer at least 6 months after the first surgery. In this multicentric study, we collected healthy mucosa surrounding the rectal cancer. A panel of immune markers was retrospectively investigated at immunohistochemistry: CD3, CD4, CD8, CD8beta, Tbet, FoxP3, PD-L1, MSH6, and PMS2 and CD80. Immune markers within the healthy rectal mucosa were compared between patients with metachronous rectal cancer and those with a sporadic one. Sporadic rectal cancer and metachronous rectal cancer were compared. Nonparametric tests were used for small sample size comparison.
Results
A total of 412 patients with rectal cancer included in the retrospective cohort of IMMUNOREACT 1 and 2 cohorts were analyzed and 18 of them had a metachronous rectal cancer. Previously, only 4 of them had a right colon cancer while the other 14 had a previous left or sigmoid colon cancer. No mismatch repair gene deficiencies were observed in the two cohorts. In therapy-naïve patients with metachronous cancer, CD8+ T-cells infiltration was lower than that in patients with sporadic cancer (p=0.021). Moreover, in the whole cohort of patients, metachronous cancer had less frequently aa high level of CD8+ T cell infiltration than sporadic cancers (p=0.047).
Conclusion
Our study showed that, metachronous rectal cancer occurs frequently in the same site of the primitive ones suggesting a role for the cancerization field. Moreover, our data suggest that a constitutive weak cytotoxic T-cell activity may be a crucial factor, permitting the occurrence of metachronous CRC.
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