GLUT1-Positive Immune Cells at the Tumor Interface: Uncovering a Metabolic Pathway to Enhanced Survival in Colorectal Liver Metastases

Background: Glucose transporter 1 (GLUT1) is crucial for cellular energy regulation, and its elevated expression in tumor cells is associated with poor prognosis in several malignancies, including colorectal carcinoma. However, the role of GLUT1 expression in immune cells and its impact on antitumor responses remains underexplored. This study investigates the influence of GLUT1-positive immune cells within the infiltration margin of colorectal liver metastases on patient survival.

Materials and Methods: Immunohistochemical staining for GLUT1 was performed on colorectal liver metastasis tissue samples, and GLUT1 expression was correlated with patient survival data from a clinical database. Leukocytes isolated from the infiltration margin were analyzed via flow cytometry to differentiate between GLUT1-positive and GLUT1-negative CD8+TEMRA cells. The cytotoxic potential of these cells was assessed based on GLUT1 expression and granzyme B levels.

Results: Increased GLUT1 expression within the infiltration margin was significantly associated with prolonged patient survival (p=0.011), independent of tumor proliferation rate. This survival advantage was most notable in patients with solitary liver metastases. Flow cytometry revealed a higher frequency of GLUT1-positive CD8+TEMRA cells, with a trend toward increased granzyme B expression, although this did not reach statistical significance (p=0.06).

Conclusion: GLUT1 expression in immune cells at the tumor-host interface may enhance antitumor immune responses, possibly through increased cytotoxicity of CD8+TEMRA cells. These findings suggest that GLUT1 could serve as a valuable prognostic marker and a potential target for therapeutic strategies aimed at boosting immune-mediated tumor suppression in colorectal liver metastases.

Publication History

Article published online:
20 January 2025