Stroma AReactive Invasion Front Areas (SARIFA), tumour immune microenvironment, and survival in colorectal cancer
Menée à partir d'échantillons tumoraux et de données portant sur 1 876 patients atteints d'un cancer colorectal, cette étude évalue l'association entre le statut SARIFA (présence d'un contact direct entre un groupe de cellules cancéreuses et des cellules adipeuses au niveau de la marge d'invasion tumorale), la densité de cellules immunitaires antitumorigènes dans le microenvironnement tumoral et la survie des patients
Background : SARIFA (Stroma AReactive Invasion Front Areas), defined as the direct contact between a tumour cell cluster and adipose cells at the invasion margin, has been proposed as a prognostic marker in gastrointestinal cancers. We hypothesized that SARIFA is associated with an immunosuppressive tumour microenvironment.
Methods : SARIFA status was evaluated in two large colorectal cancer cohorts (N = 1876). Survival analyses were performed using multivariable Cox regression. Immune cell densities were analysed utilizing multiplex and conventional immunohistochemistry combined with digital image analysis.
Results : SARIFA-positivity was independently associated with a shorter cancer-specific survival in both cohorts [Cohort 1: hazard ratio (HR) for SARIFA-positive (vs. negative) 1.75 (95% CI 1.35–2.25), P < 0.0001; Cohort 2: HR for SARIFA-positive (vs. negative) 2.09 (95% CI 1.43–3.05), P = 0.0001]. SARIFA-positivity was associated with lower densities of CD3+ T cells, CD66b+ granulocytes, M1-like macrophages, and CD14+HLA-DR+ mature monocytic cells, but higher densities of M2-like macrophages and CD14+HLA-DR- immature monocytic cells. Mean Cohen’s kappa for SARIFA evaluation between eight investigators was 0.80.
Conclusions : SARIFA status is a highly reproducible, independent prognostic factor in colorectal cancer. SARIFA-positivity is associated with lower densities of antitumourigenic immune cells and the polarisation of macrophages towards a protumourigenic M2-like phenotype.
British Journal of Cancer , article en libre accès, 2025