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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Oncogenic states dictate the prognostic and predictive connotations of intratumoral immune response
Journal for ImmunoTherapy of Cancer, Volume 8, No. 1, Article e000617, Year 2020
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Description
Background An immune active cancer phenotype typified by a T helper 1 (Th-1) immune response has been associated with increased responsiveness to immunotherapy and favorable prognosis in some but not all cancer types. The reason of this differential prognostic connotation remains unknown. Methods To explore the contextual prognostic value of cancer immune phenotypes, we applied a multimodal pan-cancer analysis among 31 different histologies (9282 patients), encompassing immune and oncogenic transcriptomic analysis, mutational and neoantigen load and copy number variations. Results We demonstrated that the favorable prognostic connotation conferred by the presence of a Th-1 immune response was abolished in tumors displaying specific tumor-cell intrinsic attributes such as high transforming growth factor-beta (TGF-β) signaling and low proliferation capacity. This observation was independent of mutation rate. We validated this observation in the context of immune checkpoint inhibition. WNT-β catenin, barrier molecules, Notch, hedgehog, mismatch repair, telomerase activity and AMPK signaling were the pathways most coherently associated with an immune silent phenotype together with mutations of driver genes including IDH1/2, FOXA2, HDAC3, PSIP1, MAP3K1, KRAS, NRAS, EGFR, FGFR3, WNT5A and IRF7. Conclusions This is the first systematic study demonstrating that the prognostic and predictive role of a bona fide favorable intratumoral immune response is dependent on the disposition of specific oncogenic pathways. This information could be used to refine stratification algorithms and prioritize hierarchically relevant targets for combination therapies. © © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
Authors & Co-Authors
Roelands, Jessica
Qatar, Doha
Sidra Medicine
Netherlands, Leiden
Leids Universitair Medisch Centrum
Hendrickx, Wouter R.L.
Qatar, Doha
Sidra Medicine
Qatar, Doha
Hamad Bin Khalifa University
Zoppoli, Gabriele
Italy, Genoa
Irccs San Martino Polyclinic Hospital
Italy, Genoa
Università Degli Studi Di Genova
Mall, Raghvendra
Qatar, Doha
Hamad Bin Khalifa University
Saad, Mohamad
Qatar, Doha
Hamad Bin Khalifa University
Curigliano, Giuseppe
Italy, Milan
Università Degli Studi Di Milano
Rinchai, Darawan
Qatar, Doha
Sidra Medicine
Decock, Julie V.
Unknown Affiliation
Delogu, Lucia Gemma
Unknown Affiliation
Chouchane, Lotfi
Unknown Affiliation
Ballestrero, Alberto
Italy, Genoa
Irccs San Martino Polyclinic Hospital
Italy, Genoa
Università Degli Studi Di Genova
Wang, Ena
Unknown Affiliation
Finetti, Pascal
Unknown Affiliation
Bertucci, François
Unknown Affiliation
Miller, Lance David
Unknown Affiliation
Galon, Jérôme
Unknown Affiliation
Marincola, Franco Maria
Unknown Affiliation
Kuppen, Peter J.K.
Netherlands, Leiden
Leids Universitair Medisch Centrum
Ceccarelli, Michele
United States, North Chicago
Abbvie
Italy, Naples
Università Degli Studi Di Napoli Federico Ii
Italy, Ariano Irpino
Biogem S.c.a.r.l.
Bedognetti, Davide
Qatar, Doha
Sidra Medicine
Qatar, Doha
Hamad Bin Khalifa University
Statistics
Citations: 50
Authors: 20
Affiliations: 9
Identifiers
Doi:
10.1136/jitc-2020-000617
ISSN:
20511426
Research Areas
Cancer