Negative immune factors might predominate local tumor immune status and promote carcinogenesis in cervical carcinoma

Abstract

Background

The disequilibrium of local immune microenvironment is an essential element during tumorigenesis.

Method

By conducting real-time polymerase chain reaction, we identified the mRNA level of immune factors, FoxP3 (forkhead box protein P3), CCL22/CCR4 (chemokine (C-C motif) ligand 22/CC chemokine receptor 4), OX40L/OX40 (tumor necrosis factor superfamily member 4/tumor necrosis factor receptor superfamily member 4) and Smad3 (SMAD family member 3) in neoplastic foci and its periphery tissues from 30 cases of squamous cervical carcinoma and 20 cases of normal cervix.

Result

The FoxP3, CCL22 and CCR4 mRNA level in local immune microenvironment of normal cervix was lower than that in cervical cancer. While OX40L, OX40 and Smad3 mRNA level profile in normal cervix was higher than that in cervical cancer. Beyond individual effect, the pairwise positive correlations were demonstrated among the mRNA level of FoxP3, CCL22 and CCR4. The mRNA level of OX40 negatively correlated with CCL22, but positively correlated with Smad3. Moreover, the mRNA level of FoxP3 and CCL22 was increased while Smad3 was decreased in cervical tissue with HPV (human papilloma virus) infection.

Conclusion

Our data yields insight into the roles of these immune factors in cervical carcinogenesis. It may therefore be that, in microenvironment of cervical squamous cell carcinoma, along with the context of HPV infection, negative immune regulators FoxP3, CCL22 and CCR4 might overwhelm positive immune factors OX40L, OX40 and Smad3, giving rise to an immunosuppressive status and promote the progression of cervical carcinogenesis.