Immune infiltrates are prognostic factors in localized gastrointestinal stromal tumors
Menée sur une cohorte de 57 patients atteints d'une tumeur stromale gastro-intestinale localisée et 10 patients atteints d'une tumeur métastatique, cette étude évalue l'intérêt des lymphocytes infiltrant les tumeurs, notamment les lymphocytes surexprimant CD3, pour le pronostic de la maladie
Cancer immunosurveillance relies on effector/memory tumor infiltrating CD8+T cells with a Th1 profile. Evidence for an NK cell-based control of human malignancies is still largely missing. The KIT tyrosine kinase inhibitor imatinib mesylate (IM) markedly prolongs the survival of patients with gastrointestinal stromal tumors (GIST) by direct effects on tumor cells, as well as by indirect immunostimulatory effects on T and NK cells. Here, we investigated the prognostic value of tumor-infiltrating lymphocytes expressing CD3, Foxp3 or NKp46 (NCR1) in a cohort of patients with localized GIST. We found that CD3+ TIL were highly activated in GIST and were especially enriched in areas of the tumor that conserve class I MHC expression in spite of IM treatment. High densities of CD3+ TIL predicted progression-free survival (PFS) in multivariate analyses. Moreover, GIST were infiltrated by a homogeneous subset of cytokine secreting -CD56bright (NCAM1) NK cells that accumulated in tumor foci after IM treatment. The density of the NK infiltrate independently predicted PFS and added prognostic information to the Miettinen score, as well as to the KIT mutational status. NK and T lymphocytes preferentially distributed to distinct areas of tumor sections and probably contributed independently to GIST immunosurveillance. These findings encourage the prospective validation of immune biomarkers for optimal risk stratification of GIST patients.
Cancer Research , résumé, 2013