دورية أكاديمية

A balance score between immune stimulatory and suppressive microenvironments identifies mediators of tumour immunity and predicts pan-cancer survival

التفاصيل البيبلوغرافية
العنوان: A balance score between immune stimulatory and suppressive microenvironments identifies mediators of tumour immunity and predicts pan-cancer survival
المؤلفون: Turan T., Kongpachith S., Halliwill K., Roelands J., Hendrickx W., Marincola F. M., Hudson T. J., Jacob H. J., Bedognetti D., Samayoa J., Ceccarelli M.
المساهمون: Turan, T., Kongpachith, S., Halliwill, K., Roelands, J., Hendrickx, W., Marincola, F. M., Hudson, T. J., Jacob, H. J., Bedognetti, D., Samayoa, J., Ceccarelli, M.
سنة النشر: 2021
المجموعة: IRIS Università degli Studi di Napoli Federico II
مصطلحات موضوعية: Cohort Studie, Databases, Genetic, Human, Immune Checkpoint Inhibitor, Immunologic Surveillance, Lymphocytes, Tumor-Infiltrating, Neoplasm, Survival Analysi, Tumor Microenvironment
الوصف: 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 × 10−36). 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.
نوع الوثيقة: article in journal/newspaper
اللغة: English
العلاقة: info:eu-repo/semantics/altIdentifier/wos/WOS:000638266800001; volume:124; issue:4; firstpage:760; lastpage:769; numberofpages:10; journal:BRITISH JOURNAL OF CANCER; http://hdl.handle.net/11588/880307Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85094946669
DOI: 10.1038/s41416-020-01145-4
الإتاحة: https://doi.org/10.1038/s41416-020-01145-4Test
http://hdl.handle.net/11588/880307Test
رقم الانضمام: edsbas.48898CC6
قاعدة البيانات: BASE