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Publication
Cell-programmed nutrient partitioning in the tumour microenvironment.
Authors Reinfeld BI, Madden MZ, Wolf MM, Chytil A, Bader JE, Patterson AR, Sugiura A,
Cohen AS, Ali A, Do BT, Muir A, Lewis CA, Hongo RA, Young KL, Brown RE, Todd VM,
Huffstater T, Abraham A, O'Neil RT, Wilson MH, Xin F, Tantawy MN, Merryman WD,
Johnson RW, Williams CS, Mason EF, Mason FM, Beckermann KE, Vander Heiden MG,
Manning HC, Rathmell JC, Rathmell WK
Submitted By Submitted Externally on 12/3/2021
Status Published
Journal Nature
Year 2021
Date Published 5/1/2021
Volume : Pages 593 : 282 - 288
PubMed Reference 33828302
Abstract Cancer cells characteristically consume glucose through Warburg metabolism1, a
process that forms the basis of tumour imaging by positron emission tomography
(PET). Tumour-infiltrating immune cells also rely on glucose, and impaired
immune cell metabolism in the tumour microenvironment (TME) contributes to
immune evasion by tumour cells2-4. However, whether the metabolism of immune
cells is dysregulated in the TME by cell-intrinsic programs or by competition
with cancer cells for limited nutrients remains unclear. Here we used PET
tracers to measure the access to and uptake of glucose and glutamine by specific
cell subsets in the TME. Notably, myeloid cells had the greatest capacity to
take up intratumoral glucose, followed by T cells and cancer cells, across a
range of cancer models. By contrast, cancer cells showed the highest uptake of
glutamine. This distinct nutrient partitioning was programmed in a
cell-intrinsic manner through mTORC1 signalling and the expression of genes
related to the metabolism of glucose and glutamine. Inhibiting glutamine uptake
enhanced glucose uptake across tumour-resident cell types, showing that
glutamine metabolism suppresses glucose uptake without glucose being a limiting
factor in the TME. Thus, cell-intrinsic programs drive the preferential
acquisition of glucose and glutamine by immune and cancer cells, respectively.
Cell-selective partitioning of these nutrients could be exploited to develop
therapies and imaging strategies to enhance or monitor the metabolic programs
and activities of specific cell populations in the TME.




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