Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 116, Issue 18, Pages 9020-9029Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1818210116
Keywords
|cancer stemness; antitumor immunity; intratumoral heterogeneity
Categories
Funding
- BC Cancer Foundation
- Canadian Cancer Society
- Canada's Networks and Centres of Excellence
- Canadian Institutes of Health Research
- Terry Fox Research Institute
- Cancer Research Society
- Vanier Canada Graduate Scholarship
- Canadian Institutes of Health Research Postdoctoral fellowships
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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 cellintrinsic 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.
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