Gaya Spolverato, Matteo Fassan, Melania Scarpa, Astghik Stepanyan, Ottavia De Simoni, Federico Scognamiglio, Valentina Chiminazzo, Clarissa De Nardi, Giulia Tamponi, Silvia Negro, Imerio Angriman, Andromachi Kotsafti, Cesare Ruffolo, Chiara Vignotto, Maurizio Zizzo, Francesco Marchegiani, Luca Facci, Francesca Bergamo, Stefano Brignola, Gianluca Businello, Vincenza Guzzardo, Luca Dal Santo, Roberta Salmaso, Carlotta Ceccon, Marco Massani, Anna Pozza, Ivana Cataldo, Tommaso Stecca, Angelo Paolo Dei Tos, Vittorina Zagonel, Pierluigi Pilati, Boris Franzato, Antonio Scapinello, Giovanni Pirozzolo, Alfonso Recordare, Roberto Merenda, Giovanni Bordignon, Licia Laurino, Silvio Guerriero, Chiara Romiti, Giuseppe Portale, Chiara Cipollari, Salvatore Candioli, Laura Gavagna, Giulia Pozza, Mario Godina, Isabella Mondi, Giulia Noaro, Monica Ortenzi, Mario Guerrieri, Giovanni Tagliente, Monica Tomassi, Umberto Tedeschi, Andrea Porzionato, Marco Agostini, Isacco Maretto, Quoc Riccardo Bao, Francesco Cavallin, Barbara Di Camillo, Romeo Bardini, Ignazio Castagliuolo, Salvatore Pucciarelli, Marco Scarpa, Giulia Capelli, Michela Campi, Luca Saadeh, Dario Parini, Daniela Prando, Beatrice Salmaso, Gianluca Buzzi, Loretta Di Cristofaro, Corrado Da Lio, Giulia Becherucci, Fabio Ricagna, Roberto Cola,

IMMUNOREACT 6: weak immune surveillance characterizes early-onset rectal cancer

  • Surgery
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Abstract Background Colon cancer in young patients is often associated with hereditary syndromes; however, in early-onset rectal cancer, mutations of these genes are rarely observed. The aim of this study was to analyse the features of the local immune microenvironment and the mutational pattern in early-onset rectal cancer. Methods Commonly mutated genes were analysed within a rectal cancer series from the University Hospital of Padova. Mutation frequency and immune gene expression in a cohort from The Cancer Genome Atlas (‘TCGA’) were compared and immune-cell infiltration levels in the healthy rectal mucosa adjacent to rectal cancers were evaluated in the IMMUNOlogical microenvironment in REctal AdenoCarcinoma Treatment 1 and 2 (‘IMMUNOREACT’) series. Results In the authors’ series, the mutation frequency of BRAF, KRAS, and NRAS, as well as microsatellite instability frequency, were not different between early- and late-onset rectal cancer. In The Cancer Genome Atlas series, among the genes with the most considerable difference in mutation frequency between young and older patients, seven genes are involved in the immune response and CD69, CD3, and CD8β expression was lower in early-onset rectal cancer. In the IMMUNOlogical microenvironment in REctal AdenoCarcinoma Treatment 1 and 2 series, young patients had a lower rate of CD4+ T cells, but higher T regulator infiltration in the rectal mucosa. Conclusion Early-onset rectal cancer is rarely associated with common hereditary syndromes. The tumour microenvironment is characterized by a high frequency of mutations impairing the local immune surveillance mechanisms and low expression of immune editing-related genes. A constitutively low number of CD4 T cells associated with a high number of T regulators indicates an imbalance in the immune surveillance mechanisms.

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