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. 2023 Oct 10;110(11):1490-1501.
doi: 10.1093/bjs/znad219.

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

Gaya Spolverato  1 , Matteo Fassan  2   3 , Melania Scarpa  4 , Astghik Stepanyan  1 , Ottavia De Simoni  5 , Federico Scognamiglio  1 , Valentina Chiminazzo  1 , Clarissa De Nardi  1 , Giulia Tamponi  1 , Silvia Negro  1 , Imerio Angriman  1 , Andromachi Kotsafti  4 , Cesare Ruffolo  1 , Chiara Vignotto  1 , Maurizio Zizzo  6 , Francesco Marchegiani  1 , Luca Facci  1 , Francesca Bergamo  7 , Stefano Brignola  8 , Gianluca Businello  9 , Vincenza Guzzardo  2 , Luca Dal Santo  1 , Roberta Salmaso  2 , Carlotta Ceccon  2 , Marco Massani  10 , Anna Pozza  10 , Ivana Cataldo  8 , Tommaso Stecca  10 , Angelo Paolo Dei Tos  2 , Vittorina Zagonel  7 , Pierluigi Pilati  5 , Boris Franzato  5 , Antonio Scapinello  11 , Giovanni Pirozzolo  12 , Alfonso Recordare  12 , Roberto Merenda  13 , Giovanni Bordignon  13 , Licia Laurino  14 , Silvio Guerriero  15 , Chiara Romiti  15 , Giuseppe Portale  16 , Chiara Cipollari  16 , Salvatore Candioli  17 , Laura Gavagna  17 , Giulia Pozza  12 , Mario Godina  12 , Isabella Mondi  12 , Giulia Noaro  18 , Monica Ortenzi  19 , Mario Guerrieri  19 , Giovanni Tagliente  20 , Monica Tomassi  20 , Umberto Tedeschi  20 , Andrea Porzionato  21 , Marco Agostini  1 , Isacco Maretto  1 , Quoc Riccardo Bao  1 , Francesco Cavallin  22 , Barbara Di Camillo  23 , Romeo Bardini  1 , Ignazio Castagliuolo  24 , Salvatore Pucciarelli  1 , Marco Scarpa  1 ; IMMUNOREACT Study Group
Collaborators, Affiliations

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

Gaya Spolverato et al. Br J Surg. .

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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