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Proc Natl Acad Sci U S A. 2019 Apr 30;116(18):9020-9029. doi: 10.1073/pnas.1818210116. Epub 2019 Apr 17.

Cancer stemness, intratumoral heterogeneity, and immune response across cancers.

Author information

1
Deeley Research Centre, BC Cancer, Victoria, BC V8R 6V5, Canada.
2
Department of Molecular Oncology, BC Cancer, Vancouver, BC V5Z 4E6, Canada.
3
Centre for Molecular Medicine and Therapeutics, BC Children's Hospital Research Institute, Vancouver, BC V5Z 4H4, Canada.
4
Graduate Bioinformatics Training Program, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
5
The Kinghorn Cancer Centre and Cancer Division, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia.
6
Singapore Immunology Network, Agency for Science, Technology and Research, 138648 Singapore.
7
Department of Immunology, Genetics, and Pathology, Uppsala University, 751 85 Uppsala, Sweden.
8
Department of Molecular Oncology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, 0379 Oslo, Norway.
9
Programme Cartes d'Identité des Tumeurs, Ligue Nationale Contre le Cancer, 75013 Paris, France.
10
Deeley Research Centre, BC Cancer, Victoria, BC V8R 6V5, Canada; bnelson@bccrc.ca.
11
Department of Biochemistry and Microbiology, University of Victoria, Victoria, BC V8P 3E6, Canada.
12
Department of Medical Genetics, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.

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.

KEYWORDS:

antitumor immunity; cancer stemness; intratumoral heterogeneity

PMID:
30996127
PMCID:
PMC6500180
[Available on 2019-10-17]
DOI:
10.1073/pnas.1818210116

Conflict of interest statement

The authors declare no conflict of interest.

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