Background: Previous experimental and clinical studies have shown that lactate concentrations
of 10 mM and more in solid malignant tumors may inactivate cytotoxic T cells as a major component
of the immune defense of the tumor host. Additionally, it has been demonstrated recently that glucose
depletion within cancerous tissue to concentrations of 1 mM and less may inhibit the T cellmediated
immune response, as well. To evaluate the significance of lactate accumulation compared to
glucose depletion in cancers, we have revisited previous data using the technique of induced metabolic
Bioluminescence Imaging (imBI) in various entities of human tumor xenografts and tumors in the clinic.
These tumor entities comprise squamous cell carcinomas of the cervix and of the head and neck,
ovarian cancer metastases, rectal adenocarcinomas, glioblastomas, and melanomas. Tissue lactate levels
in metastatic primary tumors were 1.5- to 2-times higher than those in non-metastatic primaries, and this
was true for both patient cancers and corresponding tumor xenografts. Immunologically relevant lactate
accumulation (≥ 10 mM) occurred in a large majority of all tumors investigated. In contrast, tumors
with average glucose concentrations of 1 mM and less were rarely found in general with the striking exception
of rectal adenocarcinomas, where 67 % of all tumors were low glucose malignancies.
Conclusion: lactate accumulation in malignant tissue may be quantitatively more relevant for the immune
escape compared to glucose depletion. However, in rectal adenocarcinomas both high lactate and
low glucose concentrations may substantially contribute to the inhibition of the immune defense.
Keywords: Induced metabolic Bioluminescence Imaging (imBI), various human tumor entities, Warburg metabolism, lactate
accumulation, glucose depletion, inhibition of cytotoxic T cells, Natural Killer (NK) cells.
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