Search

Objective: This study aims to describe cervical cancer during pregnancy (CCP) and investigate factors associated with survival outcomes., Methods: This retrospective matched study included CCP patients from May 2007 to August 2021 and matched non-pregnant cervical cancer patients (1:2) based on age (±5 years), year at diagnosis (±2 years), histological type and stage (2018 FIGO). The Kaplan-Meier method and multivariate Cox regression analyses were used to assess the impact of pregnancy and clinicopathologic factors on prognosis., Results: Thirty-eight CCP patients (stage IA to IIIC) and 76 non-pregnant patients were included. Most CCP patients were diagnosed in the first (31.6%) or second (47.4%) trimester. CCP patients had a longer waiting time than non-pregnant patients. Pregnancy continued in 42.1% (continuation of pregnancy [COP] group) and was terminated in 57.9% (termination of pregnancy [TOP] group) of patients. Survival analysis showed no significant differences in recurrence-free survival (RFS) or overall survival (OS) between pregnant and non-pregnant patients or between the COP and TOP groups. At the end of the follow-up period (range 12-178 months), 23 children born to CCP patients exhibited normal development., Conclusion: Pregnancy does not impact cervical cancer prognosis. The oncologic outcomes of the TOP and COP groups were comparable. A pregnancy-preserving strategy could be considered for managing CCP patients., (© 2023 International Federation of Gynecology and Obstetrics.)

Background: Cervical cancer (CC) is the fourth most common cancer in women worldwide. Although immunotherapy has been applied in clinical practice, its therapeutic efficacy remains far from satisfactory, necessitating further investigation of the mechanism of CC immune remodeling and exploration of novel treatment targets. This study aimed to investigate the mechanism of CC immune remodeling and explore potential therapeutic targets., Methods: We conducted single-cell RNA sequencing on a total of 17 clinical specimens, including normal cervical tissues, high-grade squamous intraepithelial lesions, and CC tissues. To validate our findings, we conducted multicolor immunohistochemical staining of CC tissues and constructed a subcutaneous tumorigenesis model in C57BL/6 mice using murine CC cell lines (TC1) to evaluate the effectiveness of combination therapy involving indoleamine 2,3-dioxygenase 1 (IDO1) inhibition and immune checkpoint blockade (ICB). We used the unpaired two-tailed Student's t-test, Mann-Whitney test, or Kruskal-Wallis test to compare continuous data between two groups and one-way ANOVA with Tukey's post hoc test to compare data between multiple groups., Results: Malignant cervical epithelial cells did not manifest noticeable signs of tumor escape, whereas lysosomal-associated membrane protein 3-positive (LAMP3 + ) dendritic cells (DCs) in a mature state with immunoregulatory roles were found to express IDO1 and affect tryptophan metabolism. These cells interacted with both tumor-reactive exhausted CD8 + T cells and CD4 + regulatory T cells, synergistically forming a vicious immunosuppressive cycle and mediating CC immune escape. Further validation through multicolor immunohistochemical staining showed co-localization of neoantigen-reactive T cells (CD3 + , CD4 + /CD8 + , and PD-1 + ) and LAMP3 + DCs (CD80 + and PD-L1 + ). Additionally, a combination of the IDO1 inhibitor with an ICB agent significantly reduced tumor volume in the mouse model of CC compared with an ICB agent alone., Conclusions: Our study suggested that a combination treatment consisting of targeting IDO1 and ICB agent could improve the therapeutic efficacy of current CC immunotherapies. Additionally, our results provided crucial insights for designing drugs and conducting future clinical trials for CC., (© 2023 The Authors. Cancer Communications published by John Wiley & Sons Australia, Ltd on behalf of SUN YAT-SEN UNIVERSITY CANCER CENTER.)