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Cancer stemness, intratumoral heterogeneity, and immune response across cancers

Abstract

Regulatory programs that control the function of stem cells are active in cancer and confer properties that promote progression and therapy resistance. However, the impact of a stem cell-like tumor phenotype ("stemness") on the immunological properties of cancer has not been systematically explored. Using gene-expression-based metrics, we evaluated the association of stemness with immune cell infiltration and genomic, transcriptomic, and clinical parameters across 21 solid cancers. We found pervasive negative associations between cancer stemness and anticancer immunity. This occurred despite high stemness cancers exhibiting increased mutation load, cancer-testis antigen expression, and intratumoral heterogeneity. Stemness was also strongly associated with cell-intrinsic suppression of endogenous retroviruses and type I IFN signaling, and increased expression of multiple therapeutically accessible immunosuppressive pathways. Thus, stemness is not only a fundamental process in cancer progression but may provide a mechanistic link between antigenicity, intratumoral heterogeneity, and immune suppression across cancers.

Type Journal
ISBN 1091-6490 (Electronic) 0027-8424 (Linking)
Authors Miranda, A.; Hamilton, P. T.; Zhang, A. W.; Pattnaik, S.; Becht, E.; Mezheyeuski, A.; Bruun, J.; Micke, P.; de Reynies, A.; Nelson, B. H.
Responsible Garvan Author Dr Swetansu Pattnaik
Publisher Name PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Published Date 2019-04-01
Published Volume 116
Published Issue 18
Published Pages 9020-9029
Status Published in-print
DOI 10.1073/pnas.1818210116
URL link to publisher's version https://www.ncbi.nlm.nih.gov/pubmed/30996127