Immunometabolism: A 'Hot' Switch for 'Cold' Pediatric Solid Tumors

Lin Xiao; Harrison Yeung; Michelle Haber; Murray D Norris; Klaartje Somers

doi:10.1016/j.trecan.2021.05.002

Immunometabolism: A 'Hot' Switch for 'Cold' Pediatric Solid Tumors

Trends Cancer. 2021 Aug;7(8):751-777. doi: 10.1016/j.trecan.2021.05.002. Epub 2021 Jun 26.

Authors

Lin Xiao¹, Harrison Yeung², Michelle Haber¹, Murray D Norris³, Klaartje Somers⁴

Affiliations

¹ Children's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales Sydney, NSW 2052, Australia; School of Women's and Children's Health, University of New South Wales Sydney, Randwick, NSW 2052, Australia.
² Children's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales Sydney, NSW 2052, Australia.
³ Children's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales Sydney, NSW 2052, Australia; School of Women's and Children's Health, University of New South Wales Sydney, Randwick, NSW 2052, Australia; University of New South Wales Centre for Childhood Cancer Research, Sydney, Australia.
⁴ Children's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales Sydney, NSW 2052, Australia; School of Women's and Children's Health, University of New South Wales Sydney, Randwick, NSW 2052, Australia. Electronic address: ksomers@ccia.org.au.

PMID: 34183305
DOI: 10.1016/j.trecan.2021.05.002

Abstract

Despite the success of immunotherapies in adult solid cancers and pediatric hematological malignancies, limited progress has been made towards implementing these strategies in pediatric solid tumors. These tumors exhibit a high potential to escape antitumor immunity, making them difficult to target by current immunotherapies. This review highlights the altered metabolic pathways in pediatric solid tumors that promote immune escape, and discusses current novel strategies targeting these pathways. We further explore how these strategies could be applied to potentiate immunotherapies for pediatric solid cancers and pose key questions yet to be addressed. Translational challenges to facilitate clinical application of antimetabolic strategies through personalized medicine are identified. We propose preclinical testing of antimetabolic approaches in combination with immunotherapies for pediatric solid cancers.

Keywords: immune cold; immunometabolism; immunotherapy; pediatric solid tumors.

Publication types

Review

MeSH terms

Age Factors
Animals
Antigens, Neoplasm / genetics
Antigens, Neoplasm / metabolism
Antimetabolites, Antineoplastic / pharmacology
Antimetabolites, Antineoplastic / therapeutic use*
Antineoplastic Combined Chemotherapy Protocols / pharmacology
Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
Cell Line, Tumor
Child
Humans
Immune Checkpoint Inhibitors / pharmacology
Immune Checkpoint Inhibitors / therapeutic use*
Immunotherapy / methods*
Metabolic Networks and Pathways / drug effects
Metabolic Networks and Pathways / genetics
Metabolic Networks and Pathways / immunology
Mutation
Neoplasms / genetics
Neoplasms / immunology
Neoplasms / therapy*
Tumor Escape / drug effects
Tumor Escape / genetics
Tumor Microenvironment / drug effects
Tumor Microenvironment / genetics
Tumor Microenvironment / immunology
Xenograft Model Antitumor Assays

Substances

Antigens, Neoplasm
Antimetabolites, Antineoplastic
Immune Checkpoint Inhibitors