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Targeting colorectal cancer and T‑cell metabolism for the treatment of colorectal cancer (Review)

  • Authors:
    • Qiangzong Yu
    • Pengbo Luan
    • Jingru Liang
    • Lixin Wang
  • View Affiliations / Copyright

    Affiliations: Department of Gastrointestinal Surgery, Yantaishan Hospital, Yantai, Shandong 264003, P.R. China
    Copyright: © Yu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 142
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    Published online on: June 2, 2026
       https://doi.org/10.3892/or.2026.9147
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Abstract

Colorectal cancer (CRC) is a malignant tumor of the digestive tract that is highly prevalent worldwide, which is associated with a poor prognosis in advanced stages and for which current treatment plans have limited efficacy. T cells serve a crucial role in immune clearance and immune evasion within the tumor microenvironment. However, tumor cells directly impair the function of T cells through nutrient competition and the release of inhibitory metabolites. Notably, targeting ‘metabolic checkpoints’ has emerged as a crucial strategy to enhance T‑cell efficacy. The present literature review summarizes the role of reprogramming glycolysis, glutaminolysis and lipid metabolism in driving immune evasion in CRC, and discusses potential intervention strategies from two perspectives: Modulating tumor metabolism and optimizing the intrinsic metabolic functions of T cells. Finally, it is proposed that stratified precision therapy based on individual metabolic profiles represents a future direction for overcoming immune heterogeneity and drug resistance in CRC.
View Figures

Figure 1

Overview of metabolic pathways
associated with colorectal cancer cells. Schematic diagram of the
major metabolic pathways contributing to malignant transformation
and the corresponding metabolic checkpoints. Metabolic enzymes
implicated in tumor initiation and growth are highlighted with red
boxes. Created with Figdraw.com. α-KG, α-ketoglutarate; ACC,
acetyl-CoA carboxylase; ACSL, acyl-CoA synthetase long-chain family
member; ACLY, ATP citrate lyase; ATP, adenosine triphosphate; Cit,
citrate; CPT1, carnitine palmitoyltransferase 1; Cys, cystine;
FABP4, fatty acid-binding protein 4; FAO, fatty acid oxidation;
FASN, fatty vacid synthase; Fru-6-P, fructose-6-phosphate; GDH,
glutamate dehydrogenase; Glc-6-P, glucose-6-phosphate; Gln,
glutamine; Glu, glutamate; GLS, glutaminase; GLUT, glucose
transporter; GPAT, glycerol-3-phosphate acyltransferase; GS,
glutamine synthetase; GSH, glutathione; HK, hexokinase; LDH,
lactate dehydrogenase; LPA, lysophosphatidic acid; OAA,
oxaloacetate; PEP, phosphoenolpyruvate; PFK, phosphofructokinase;
PFKFB, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase; PKM,
pyruvate kinase M; ROS, reactive oxygen species; SLC1A5, solute
carrier family 1 member 5; SLC7A11, solute carrier family 7 member
11; SFA, saturated fatty acid; SREBP, sterol regulatory
element-binding protein; TCA, tricarboxylic acid.

Figure 2

Differentiation and functional
evolution of Tn cells upon antigen stimulation. Following antigen
stimulation, Tn cells undergo proliferation and expansion,
differentiating into Teff cells that kill tumor cells. The
persistent presence of tumor cells can drive the conversion of Teff
cells into Tex cells. Created with Figdraw.com. Tn, naïve T; Tscm,
stem cell-like memory T; Tcm, central memory T; Tem, effector
memory T; Teff, effector T cells; Tex, exhausted T cells.
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Copy and paste a formatted citation
Spandidos Publications style
Yu Q, Luan P, Liang J and Wang L: Targeting colorectal cancer and T‑cell metabolism for the treatment of colorectal cancer (Review). Oncol Rep 56: 142, 2026.
APA
Yu, Q., Luan, P., Liang, J., & Wang, L. (2026). Targeting colorectal cancer and T‑cell metabolism for the treatment of colorectal cancer (Review). Oncology Reports, 56, 142. https://doi.org/10.3892/or.2026.9147
MLA
Yu, Q., Luan, P., Liang, J., Wang, L."Targeting colorectal cancer and T‑cell metabolism for the treatment of colorectal cancer (Review)". Oncology Reports 56.2 (2026): 142.
Chicago
Yu, Q., Luan, P., Liang, J., Wang, L."Targeting colorectal cancer and T‑cell metabolism for the treatment of colorectal cancer (Review)". Oncology Reports 56, no. 2 (2026): 142. https://doi.org/10.3892/or.2026.9147
Copy and paste a formatted citation
x
Spandidos Publications style
Yu Q, Luan P, Liang J and Wang L: Targeting colorectal cancer and T‑cell metabolism for the treatment of colorectal cancer (Review). Oncol Rep 56: 142, 2026.
APA
Yu, Q., Luan, P., Liang, J., & Wang, L. (2026). Targeting colorectal cancer and T‑cell metabolism for the treatment of colorectal cancer (Review). Oncology Reports, 56, 142. https://doi.org/10.3892/or.2026.9147
MLA
Yu, Q., Luan, P., Liang, J., Wang, L."Targeting colorectal cancer and T‑cell metabolism for the treatment of colorectal cancer (Review)". Oncology Reports 56.2 (2026): 142.
Chicago
Yu, Q., Luan, P., Liang, J., Wang, L."Targeting colorectal cancer and T‑cell metabolism for the treatment of colorectal cancer (Review)". Oncology Reports 56, no. 2 (2026): 142. https://doi.org/10.3892/or.2026.9147
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