The Role Of Mucosal-associated Invariant T Cells In The Progression Of Cervical Cancer

Object One of the most common promoters of the initiation and growth of the tumor is an immune disturbance.Numerous immune cells and inflammatory factors play an important role in the tumor-immune microenvironment.There is increasing evidence showing the importance of a dysfunctional host immune response in cervical cancer progression.Mucosal-associated invariant T(MAIT)cells are a kind of unconventional innate T cells and extremely rich in peripheral blood,lungs,liver,and other mucosal tissues.On one hand,as one of the unconventional T cells,MAIT cells can show tumor-killing ability like invariant natural killer T(i NKT)cells.On the other hand,major histocompatibility complex class I-related(MR1)molecule or IL-12/18-dependent MAIT cells might accelerate tumor advancement via inducing myeloid-derived suppressor cells(MDSCs)to tumor lesions.However,few studies investigated the correlation between these immunological events and clinical consequences in cervical cancer.Method This work comprised 9 cervical intraepithelial neoplasia(CIN)patients and 36primary cervical cancer patients.Thirty-five age-matched patients presenting only uterine leiomyoma were recruited as controls.Heparinized peripheral blood was obtained from all participants immediately before surgery.Density gradient centrifugation was used to collect peripheral blood mononuclear cells(PBMCs)and plasma.We measured frequencies of MDSCs,regulatory T(Treg)cells,and MAIT cells in PBMCs of patients via flow cytometry.ELISA was used to detect the levels of numerous inflammatory mediators in plasma from patients.Results Cervical cancer patients showed elevated production of interleukin(IL)-18 and plasma C-C chemokine ligand(CCL)3/5.Meanwhile,an accumulation of C-C chemokine receptor 5(CCR5~+)monocytic(Mo)-MDSCs and Tregs was observed.The cervical cancer group displayed increased frequencies of CD8~+,CD4~+,and highly activated CD38~+CD8~+MAIT cells,and reduction of CD4~-CD8~-(double negative,DN)and PD1(CD279~+)DN MAIT cells.Importantly,it was demonstrated that MAIT cells were positively related to Mo-MDSCs.Furthermore,an elevated concentration of PD1(CD279~+)DN MAIT cells was significantly related to increased progression-free survival of patients with cervical cancer.Conclusions In conclusion,our study reveals a complex association between chronic inflammation,MDSCs,MAIT cells,and disease progression in cervical cancer and cervical intraepithelial neoplasia.The results suggest that the combined action of Mo-MDSCs and MAIT cells might be associated with the progression of cervical cancer,and high levels of DN MAIT cells might have a protective role in cervical cancer patients.