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Impaired antitumor immunity or induced immunosuppression in the tumor microenvironment contributes significantly to tumor progression and resistance to immunotherapy. It is becoming increasingly recognized that dynamic metabolic programming orchestrates appropriate immune responses, whereas incorrect metabolic reprogramming may underlie aberrant immune remodeling. Furthermore, pathways that control cellular metabolism and immune cell function by transcriptional and post‑transcriptional mechanisms are intimately interlinked, including hypo-xia‑inducible factor 1α, c‑Myc and phosphatidylinositol 3‑kinase/protein kinase B/mammalian target of rapamycin signaling. Immunometabolism is an emerging research field involving investigation of the interaction between immunological and metabolic processes. It is likely that high levels of nutrient competition and metabolic interplay exist between tumor cells and infiltrating immune cells in the local tumor milieu, which consequently leads to a reduction in antitumor immunity or immune cell dysfunction. Recently, a metabolic molecular mechanism responsible for the tumorigenic capacity of cluster of differentiation (CD)147, which exhibits high expression on the surface of various malignant tumor cells and is associated with tumor progression via multiple non‑metabolic molecular mechanisms, was identified. The aim of the present review was to focus on the glycolytic mechanism mediated by the upregulation of CD147 in tumors and tumor‑imposed metabolic restrictions on tumor‑infiltrating immune cells, and the consequent immunological hyporesponsiveness. Cellular metabolism is becoming increasingly acknowledged as a key regulator of T‑cell function, specification and fate, and the manipulation of metabolic programming may elucidate therapeutic options for immunological disorders and tumor immunotherapy.

Hepatocellular carcinoma (HCC) is a major health problem worldwide. CD147 has been reported to be overexpressed in HCC and blocking CD147 expression can decrease tumor growth. (131)I is often used in combination with other drugs to treat HCC and yields positive results. In this study, we combined the (131)I and CD147 monoclonal antibody to treat HCC in a rabbit VX2 animal model. In the (131)I-labeled CD147 antibody ((131)I-CD147-Ab) treatment group, the animals lived considerably longer than the animals in the other treatment groups. Metastasis and tumor growth in the (131)I-CD147-Ab treatment group were also inhibited. MMP2 and CD31 expression were significantly lower in the treatment group, whereas Tunel staining was overexpressed. These findings suggest that (131)I-CD147-Ab is a promising drug in the treatment of HCC, by inhibiting metastasis and growth and by decreasing the expression of MMP2 and CD31 or by inducing tumor necrosis. After testing the biochemical parameters, (131)I-CD147-Ab caused fewer side-effects in the animals.

Extracellular matrix metalloproteinase inducer (EMMPRIN) is a transmembrane glycoprotein that is involved in tumor invasion by stimulating matrix metalloproteinase (MMP) expression. Our previous immunohistochemical study found that the expression of EMMPRIN in salivary adenoid cystic carcinoma (SACC) was positively correlated with tumor perineural and perivascular invasion. The present study was designed to further investigate the role of EMMPRIN in the invasion of SACC. Western blot results showed that EMMPRIN was upregulated in the highly metastatic SACC cell line SACC-LM, compared to SACC-83, a SACC cell line with low metastatic ability. Blocking of EMMPRIN by its antibody significantly decreased the adhesion, secretion of MMP-2 and MMP-9, and invasion activity of SACC-LM cells in vitro (P<0.01). Co-cultures of SACC-LM cells with fibroblasts significantly produced elevated levels of MMP-2 and MMP-9, and promoted the in vitro invasion activity of SACC-LM cells, compared with cultures of SACC-LM cells alone (P<0.01). These results indicate that EMMPRIN may play an important role in the invasion of SACC by stimulating the expression of MMP-2 and MMP-9 in tumor and stromal cells.

Extracellular matrix metalloproteinase inducer (EMMPRIN) is a member of the immunoglobulin superfamily of adhesion molecules and has a role in the activation of several matrix metalloproteinases (MMPs). We evaluated whether EMMPRIN expression is related to tumor progression and patient outcome in human endometrial carcinoma. Paraffin-embedded surgical tissue samples from 112 patients with endometrial carcinoma were stained with anti-EMMPRIN antibody (monoclonal antibody 12C3:MoAb 12C3) for immunohistochemical analysis. EMMPRIN protein was expressed in cancerous lesions with the incidence of 97.3% (109 of 112 cases), but not in normal lesions. The scores determined by the combination of intensity and pattern of EMMPRIN staining in cancer cells correlated significantly with various histopathological risk factors: advanced stage, P=0.001; poorly differentiated carcinoma, P<0.001; lymph node metastasis, P=0.002; and lymphatic vessel infiltration, P=0.027. More importantly, recurrence-free survival was shortened in patients with higher EMMPRIN scores (HR, 3.08; 95% CI, 1.32-7.19; P=0.01). These results suggest that measurement of EMMPRIN expression with simple immunohistochemical staining may enhance the understanding of the pathophysiology of endometrial carcinoma.