Warburg phenotype in renal cell carcinoma: high expression of glucose-transporter 1 (GLUT-1) correlates with low CD8+ T-cell infiltration in the tumor

摘要: Many tumor cells are characterized by a dysregulated glucose metabolism associated with increased glycolysis in the presence of oxygen (“Warburg Effect”). Here, we analyzed for first time possible link between and immune cell infiltration renal carcinoma (RCC). RCC specimens revealed highly significant increase expression lactate dehydrogenase A (LDHA) glucose-transporter 1 (GLUT-1) compared to corresponding normal kidney tissue on mRNA level. Accordingly, lines different origin such as RCC, melanoma hepatocellular strongly expressed LDHA GLUT-1 their nonmalignant counterparts. In line this finding, secreted high amounts lactate. High LDH5, tetramer 4 subunits, was confirmed microarray analysis 249 specimens. Overall, 55/79 (69.6%) 46/71 (64.7%) cases clear showed constitutive, but heterogeneous respectively. The number CD3+, CD8+ FOXP3+ T significantly elevated lesions epithelium, effector molecules granzyme B perforin were decreased infiltrating cells. Of interest, further an inverse correlation lesions. Together, our data suggest that accelerated is low Targeting may represent interesting tool improve efficacy specific immunotherapeutic approaches RCC.