A balance score between immune stimulatory and suppressive microenvironments identifies mediators of tumour immunity and predicts pan-cancer survival
Menée à partir de données du projet "The Cancer Genome Atlas" puis validée à partir de données de la base "Gene Expression Omnibus" portant sur 7 623 patients atteints d'un cancer, cette étude met en évidence l'intérêt d'un score, basé sur l'expression de gènes impliqués dans les mécanismes de stimulation immunitaire et l'expression de gènes impliqués dans les mécanismes immunosuppresseurs, pour prédire la survie des patients
Background : The balance between immune-stimulatory and immune-suppressive mechanisms in the tumour microenvironment is associated with tumour rejection and can predict the efficacy of immune checkpoint-inhibition therapies.
Methods : We consider the observed differences between the transcriptional programmes associated with cancer types where the levels of immune infiltration predict a favourable prognosis versus those in which the immune infiltration predicts an unfavourable prognosis and defined a score named Mediators of Immune Response Against Cancer in soLid microEnvironments (MIRACLE). MIRACLE deconvolves T cell infiltration, from inhibitory mechanisms, such as TGF
β, EMT and PI3Kγ signatures.
Results
:
Our score outperforms current state-of-the-art immune signatures as a predictive marker of survival in TCGA (n
= 9305, HR: 0.043, p value: 6.7 × 10
−
36). In a validation cohort (n = 7623), MIRACLE predicts better survival compared to other immune metrics (HR: 0.1985, p value: 2.73 × 10
−
38). MIRACLE also predicts response to checkpoint-inhibitor therapies (n = 333). The tumour-intrinsic factors inversely associated with the reported score such as EGFR, PRKAR1A and MAP3K1 are frequently associated with immune-suppressive phenotypes.
Conclusions : The association of cancer outcome with the level of infiltrating immune cells is mediated by the balance of activatory and suppressive factors. MIRACLE accounts for this balance and predicts favourable cancer outcomes.
British Journal of Cancer , résumé, 2020