IMMUNOREACT 13: immune features of healthy rectal mucosa as predictors of invasion risk in stage II rectal cancer

Résumé fourni par la source

Vascular, lymphatic, and perineural invasion (VELIPI) are critical prognostic features in stage II rectal cancer (RC), guiding decisions about adjuvant therapy1,2. Although tumour-intrinsic determinants of VELIPI are well characterized3,4, the role of the constitutive immune microenvironment in tumour-adjacent, non-neoplastic mucosa remains largely unexplored. In prior work from the IMMUNOREACT consortium5, weak immune surveillance was shown to characterize early-onset rectal cancer, further supporting the concept that host immunity influences disease behaviour. Thus, we investigated whether mucosal immune profiling could identify host-related factors associated with early invasive behaviour. We performed a multicentre retrospective analysis of 153 patients with stage II RC enrolled in the IMMUNOREACT 1 and 2 cohorts (NCT04915326, NCT04917263) (Fig. S1 and Table 1). Mucosal biopsies, obtained 3–15 cm proximal to the tumour, were analysed using immunohistochemistry (IHC), flow cytometry, and transcriptomic profiling (Supplementary Methods). Patients were stratified by VELIPI status and treatment history (therapy-naïve or post-neoadjuvant therapy). Genetic and transcriptomic data from The Cancer Genome Atlas (TCGA) served as an external reference. Notably, while TCGA reflects tumour mucosa from therapy-naïve patients, our study focused exclusively on histologically normal mucosa.

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