AI Article Synopsis

  • The study highlights the importance of immune balance in tumors, showing that how immune cells interact can impact cancer treatment success.
  • Researchers developed a scoring system called MIRACLE that distinguishes beneficial T cell activity from suppressive mechanisms in various cancers.
  • MIRACLE outperformed existing methods in predicting survival rates and responses to cancer therapies in large patient populations, emphasizing its potential as a useful tool in oncology.

Article Abstract

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 TGFβ, 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). In a validation cohort (n = 7623), MIRACLE predicts better survival compared to other immune metrics (HR: 0.1985, p value: 2.73 × 10). 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884411PMC
http://dx.doi.org/10.1038/s41416-020-01145-4DOI Listing

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