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eSymposia | Advances in Cancer Immunotherapy


Cancer stemness, intratumoral heterogeneity, and immune response across cancers


Aug 17, 2020 12:00am ‐ Aug 17, 2020 12:00am

Description

Cancer stemness, intratumoral heterogeneity, and immune response across cancers. The exclusion of immune cells from the tumor microenvironment has been associated with poor prognosis in the majority of cancers. 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. Our work suggests that targeting the stemness phenotype in cancer will promote immune cell infiltration and render tumors more responsive to immune control. Alex Miranda*1, Phineas T Hamilton*1, Allen W Zhang2,3,4, Swetansu Pattnaik5, Etienne Becht6, Artur Mezheyeuski7, Jarle Bruun8, Patrick Micke7, Aurélien De Reynies9, Brad H Nelson10, 11 1 Deeley Research Centre, BC Cancer, Victoria, BC, V8R 6V5, Canada 2 Department of Molecular Oncology, BC Cancer, Vancouver, BC V5Z 4E6, Canada 3 BC Children's Hospital Research, 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, 370 Victoria St, Darlinghurst, NSW, Australia. 6 Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Singapore 7 Dept. of Immunology, Genetics and Pathology, Uppsala University, Uppsala, 751 85, Sweden 8 Department of Molecular Oncology, Institute for Cancer Research, the Norwegian Radium Hospital, Oslo University Hospital, Ullernchausseen 70, 0379 Oslo, Norway 9 Programme "Cartes d'Identité des Tumeurs" (CIT), Ligue Nationale Contre le Cancer, 14, rue Corvisart, 75013, Paris, France. 10 Department of Biochemistry and Microbiology, University of Victoria, Victoria, BC, V8P 3E6, Canada 11 Department of Medical Genetics, University of British Columbia, Vancouver, BC, V6T 1Z3, Canada. * These authors contributed equally to this work

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