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<p>The tumor microenvironment (TME) is a metabolically dynamic niche characterized by active metabolic crosstalk between tumor cells and various stromal and immune cell subsets, which critically influences tumor progression and therapeutic outcomes. Within this ecosystem, solute carrier (SLC) transporters are gatekeepers that mediate the transport of a wide range of metabolites, including nutrients, ions, and signaling molecules, across cellular membranes. SLC transporters have emerged as active regulators of TME composition and intercellular communication, representing promising yet underexplored therapeutic targets in cancer. This review highlights the central role of SLC transporters in orchestrating the competitive uptake of nutrients and the exchange of oncometabolites, thereby modulating immune responses, angiogenesis, and metabolic adaptation in the TME. By outlining strategies targeting SLC transporters for cancer therapy, this review also underscores the emerging potential of SLC transporters as therapeutic targets and offers a renewed perspective on targeting TME metabolism.</p>

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Solute carrier transporters as metabolic gatekeepers in tumor-microenvironment crosstalk

  • 期刊论文

  • 发表日期：

    2026年5月18日

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  • Zi-han Zhang,
  • Zi-yi Ding,
  • Luo-yi Chen,
  • Yi-xian Fu,
  • Min Huang

摘要

The tumor microenvironment (TME) is a metabolically dynamic niche characterized by active metabolic crosstalk between tumor cells and various stromal and immune cell subsets, which critically influences tumor progression and therapeutic outcomes. Within this ecosystem, solute carrier (SLC) transporters are gatekeepers that mediate the transport of a wide range of metabolites, including nutrients, ions, and signaling molecules, across cellular membranes. SLC transporters have emerged as active regulators of TME composition and intercellular communication, representing promising yet underexplored therapeutic targets in cancer. This review highlights the central role of SLC transporters in orchestrating the competitive uptake of nutrients and the exchange of oncometabolites, thereby modulating immune responses, angiogenesis, and metabolic adaptation in the TME. By outlining strategies targeting SLC transporters for cancer therapy, this review also underscores the emerging potential of SLC transporters as therapeutic targets and offers a renewed perspective on targeting TME metabolism.