Abstract
The chemokine CCL22 recruits regulatory T (T-reg) cells into tumor tissues and is expressed in many human tumors. However, the prognostic role of CCL22 in cervical cancer (CC) has not been determined. This study retrospectively analyzed the clinical significance of the expression of CCL22 and FOXP3 in 230 cervical cancer patients. Immunohistochemical staining analyses of CCL22 and FOXP3 were performed with a tissue microarray. Double immunofluorescence staining, cell coculture, and ELISA were used to determine CCL22 expressing cells and mechanisms. The higher number of infiltrating CCL22+ cells (CCL22high) group was associated with lymph node metastasis (p = 0.004), Fédération Internationale de Gynécologie et d’Obstétrique (FIGO) stages (p = 0.010), therapeutic strategies (p = 0.007), and survival status (p = 0.002). The number of infiltrating CCL22+ cells was positively correlated with that of infiltrating FOXP3+ cells (r = 0.210, p = 0.001). The CCL22high group had a lower overall survival rate (OS), compared to the CCL22low group (p = 0.001). However, no significant differences in progression free survival (PFS) were noted between the two groups. CCL22high was an independent predictor of shorter OS (HR, 4.985; p = 0.0001). The OS of the combination group CCL22highFOXP3high was significantly lower than that of the combination group CCL22lowFOXP3low regardless of the FIGO stage and disease subtype. CCL22highFOXP3high was an independent indictor of shorter OS (HR, 5.284; p = 0.009). The PFS of group CCL22highFOXP3high was significantly lower than that of group CCL22lowFOXP3low in cervical adenocarcinoma, but CCL22highFOXP3high was not an independent indicator (HR, 3.018; p = 0.068). CCL22 was primarily expressed in M2-like macrophages in CC and induced by cervical cancer cells. The findings of our study indicate that cervical cancer patients with elevated CCL22+ infiltrating cells require more aggressive treatment. Moreover, the results provide a basis for subsequent, comprehensive studies to advance the design of immunotherapy for cervical cancer.
Highlights
Cervical cancer is the second most prevalent tumor in developing countries and the fourth most common cause of cancer-related deaths among women
We found that C motif chemokine ligand 22 (CCL22) expressed in CC cells was significantly associated with the disease subtypes (p < 0.05)
We found that the overall survival rate (OS) of CCL22high FOXP3low and CCL22high FOXP3high groups were significantly lower than those of the CCL22low FOXP3low group in Fédération Internationale de Gynécologie et d’Obstétrique (FIGO) stage I–IIA (p = 0.001, p = 0.013, respectively)
Summary
Cervical cancer is the second most prevalent tumor in developing countries and the fourth most common cause of cancer-related deaths among women. Cancers 2019, 11, 2004 including economic conditions, genetic factors, endocrine [3], and immunity play significant role in the progression of cervical cancer. High-risk human papilloma virus is the primary cause of cervical cancer (CC) [4]. Immunosuppression states like infection with HIV [5] or taking immunosuppressive drugs [6] increases susceptibility to HPV infection and which subsequently causes cervical cancer. The current cervical cancer treatments include surgery, chemotherapy, and radiotherapy, but these are not effective for the management of advanced local cervical cancer, metastatic and recurrent tumors [7]. The use of Pembrolizumab, a PD-1 inhibitor, in the later-staged and recurrent CC was authorized [8].
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
