Anderson, N. M. & Simon, M. C. The tumor microenvironment. Curr. Biol. 30, R921–R925 (2020).

CAS  Article  Google Scholar 

Balkwill, F. R., Capasso, M. & Hagemann, T. The tumor microenvironment at a glance. J. Cell Sci. 125, 5591–5596 (2012).

CAS  Article  Google Scholar 

García-Cañaveras, J. C. & Lahoz, A. Tumor microenvironment-derived metabolites: a guide to find new metabolic therapeutic targets and biomarkers. Cancers 13, 3230 (2021).

Article  Google Scholar 

Bunse, L. et al. Suppression of antitumor T cell immunity by the oncometabolite (R)-2-hydroxyglutarate. Nat. Med. 24, 1192–1203 (2018).

CAS  Article  Google Scholar 

Allard, B., Beavis, P. A., Darcy, P. K. & Stagg, J. Immunosuppressive activities of adenosine in cancer. Curr. Opin. Pharmacol. 29, 7–16 (2016).

CAS  Article  Google Scholar 

Labadie, B. W., Bao, R. & Luke, J. J. Reimagining IDO pathway inhibition in cancer immunotherapy via downstream focus on the tryptophan-kynurenine-aryl hydrocarbon axis. Clin. Cancer Res. J. Am. Assoc. Cancer Res. 25, 1462–1471 (2019).

CAS  Article  Google Scholar 

Kilgour, M. K. et al. 1-Methylnicotinamide is an immune regulatory metabolite in human ovarian cancer. Sci. Adv. 7, eabe1174 (2021).

CAS  Article  Google Scholar 

Rush, A. et al. Research perspective on utilizing and valuing tumor biobanks. Biopreserv. Biobank. 17, 219–229 (2019).

Article  Google Scholar 

Agrawal, L., Engel, K. B., Greytak, S. R. & Moore, H. M. Understanding preanalytical variables and their effects on clinical biomarkers of oncology and immunotherapy. Semin. Cancer Biol. 52, 26–38 (2018).

CAS  Article  Google Scholar 

Ma, E. H. et al. Metabolic profiling using stable isotope tracing reveals distinct patterns of glucose utilization by physiologically activated CD8+ T cells. Immunity 51, 856–870.e5 (2019).

CAS  Article  Google Scholar 

Binek, A. et al. Flow cytometry has a significant impact on the cellular metabolome. J. Proteome Res. 18, 169–181 (2019).

CAS  PubMed  Google Scholar 

Llufrio, E. M., Wang, L., Naser, F. J. & Patti, G. J. Sorting cells alters their redox state and cellular metabolome. Redox Biol. 16, 381–387 (2018).

CAS  Article  Google Scholar 

DeVilbiss, A. W. et al. Metabolomic profiling of rare cell populations isolated by flow cytometry from tissues. eLife 10, e61980 (2021).

CAS  Article  Google Scholar 

Hirayama, A. et al. Effects of processing and storage conditions on charged metabolomic profiles in blood. Electrophoresis 36, 2148–2155 (2015).

CAS  Article  Google Scholar 

Siska, P. J. et al. Mitochondrial dysregulation and glycolytic insufficiency functionally impair CD8 T cells infiltrating human renal cell carcinoma. JCI Insight 2, 93411 (2017).

Article  Google Scholar 

Ho, P.-C. et al. Phosphoenolpyruvate Is a Metabolic Checkpoint of Anti-tumor T. Cell Responses Cell 162, 1217–1228 (2015).

CAS  PubMed  Google Scholar 

Scharping, N. E. et al. The tumor microenvironment represses T cell mitochondrial biogenesis to drive intratumoral t cell metabolic insufficiency and dysfunction. Immunity 45, 374–388 (2016).

CAS  Article  Google Scholar 

Baumann, T. et al. Regulatory myeloid cells paralyze T cells through cell–cell transfer of the metabolite methylglyoxal. Nat. Immunol. 21, 555–566 (2020).

CAS  Article  Google Scholar 

Reinfeld, B. I. et al. Cell-programmed nutrient partitioning in the tumour microenvironment. Nature 593, 282–288 (2021).

CAS  Article  Google Scholar 

Sinclair, L. V., Barthelemy, C. & Cantrell, D. A. Single cell glucose uptake assays: a cautionary tale. Immunometabolism 2, e200029 (2020).

Article  Google Scholar 

Xu, H. et al. Cyanine-based 1-amino-1-deoxyglucose as fluorescent probes for glucose transporter mediated bioimaging. Biochem. Biophys. Res. Commun. 474, 240–246 (2016).

CAS  Article  Google Scholar 

Dettmer, K., Aronov, P. A. & Hammock, B. D. Mass spectrometry-based metabolomics. Mass Spectrom. Rev. 26, 51–78 (2007).

CAS  Article  Google Scholar 

Zhang, J. et al. Chapter Nineteen - 13C isotope-assisted methods for quantifying glutamine metabolism in cancer cells. in Methods in Enzymology (eds Galluzzi, L. & Kroemer, G.) 542, 369–389 (Academic Press, 2014).

Yuan, M. et al. Ex vivo and in vivo stable isotope labelling of central carbon metabolism and related pathways with analysis by LC–MS/MS. Nat. Protoc. 14, 313–330 (2019).

CAS  Article  Google Scholar 

Pang, Z. et al. MetaboAnalyst 5.0: narrowing the gap between raw spectra and functional insights. Nucleic Acids Res. 49, W388–W396 (2021).

CAS  Article  Google Scholar 

Ritchie, M. E. et al. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 43, e47 (2015).

Article  Google Scholar 

Smyth, G. K. limma: Linear Models for Microarray Data. in Bioinformatics and Computational Biology Solutions Using R and Bioconductor (eds Gentleman, R. et al.) 397–420 (Springer, 2005).

Sheldon, R. D., Ma, E. H., DeCamp, L. M., Williams, K. S. & Jones, R. G. Interrogating in vivo T-cell metabolism in mice using stable isotope labeling metabolomics and rapid cell sorting. Nat. Protoc. 16, 4494–4521 (2021).

CAS  Article  Google Scholar 

Mullen, A. R. et al. Oxidation of alpha-ketoglutarate is required for reductive carboxylation in cancer cells with mitochondrial defects. Cell Rep. 7, 1679–1690 (2014).

CAS  Article  Google Scholar 

Haukaas, T. H. et al. Impact of freezing delay time on tissue samples for metabolomic studies. Front. Oncol. 6, 17 (2016).

Article  Google Scholar 

Xiao, B., Deng, X., Zhou, W. & Tan, E.-K. Flow cytometry-based assessment of mitophagy using MitoTracker. Front. Cell. Neurosci. 10, 76 (2016).

Article  Google Scholar 

Park, L. M., Lannigan, J. & Jaimes, M. C. OMIP-069: forty-color full spectrum flow cytometry panel for deep immunophenotyping of major cell subsets in human peripheral blood. Cytom. A 97, 1044–1051 (2020).

CAS  Article  Google Scholar 

Brummelman, J. et al. Development, application and computational analysis of high-dimensional fluorescent antibody panels for single-cell flow cytometry. Nat. Protoc. 14, 1946–1969 (2019).

CAS  Article  Google Scholar 

Darzi, Y., Letunic, I., Bork, P. & Yamada, T. iPath3.0: interactive pathways explorer v3. Nucleic Acids Res. 46, W510–W513 (2018).

CAS  Article  Google Scholar