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Archive > Volume 32 Issue 6 > 2025,32(6):570-578. DOI:10.3872/j.issn.1007-385X.2025.06.002 Prev Next
Basic Research
Id2 regulates the metabolic reprogramming of Tcm cells through the PI3K/AKT pathway to inhibit colorectal cancer cell growth
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Abstract:
[Abstract] Objective: To investigate the role of inhibitor of differentiation 2 (Id2) in inducing the generation of central memory T (Tcm) cells and enhancing the anti-tumor persistence of T cells. Methods: CD8+ na?ve T cells were sorted with magnetic beads and then co-cultured with carcinoembryonic antigen (CEA)-loaded dendritic cells (DCs). These cells were induced into effector T (Teff) or Tcm cells by interleukin-2 (IL-2) or IL-7/15/21/23, respectively. The mRNA and protein expression of Id2 and Id3 in T cells were detected using qPCR and WB, respectively. Id2 gene in T cells was knocked down using lentivirus, and the T cell memory phenotype was analyzed by flow cytometry. The expression of PI3K/AKT pathway-related proteins was examined by WB. The extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) were assessed using a Seahorse extracellular flux analyzer. A zebrafish colorectal cancer HCT116 xenograft model was employed to analyze the anti-tumor differences between Teff and Tcm cells. The effect of Id2 gene knockdown in Tcm cells (Tcm-shId2) on the growth inhibition of secondary xenografts was also observed. Results: Tcm cells exhibited high expression of Id3 mRNA (P < 0.05), whereas Teff cells showed high expression of Id2 mRNA (P < 0.001). Tcm cells with Id2 knockdown (Tcm-shId2) were successfully constructed, showing significantly upregulated Id3 expression. Knockdown of Id2 promoted the formation of Tcm cell (P < 0.05). Tcm-shId2 cells underwent metabolic reprogramming via the PI3K/AKT pathway, which effectively suppressed the growth of colorectal cancer xenografts in zebrafish and also produced significant inhibitory effects on secondary tumor growth (P < 0.01). Conclusion: Id2 gene may regulate T cell metabolism through the PI3K/AKT signaling pathway,promoting the differentiation of CD8+ T cells into Tcm cells and effectively inhibiting the growth of colorectal cancer xenografts.
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