Immune checkpoint inhibitors in advanced and recurrent/metastatic cervical cancer

Abstract

Cervical cancer (CC) poses a serious threat to women’s health. Although many early-stage patients have a good prognosis, there are still a lack of effective therapies for advanced and recurrent/metastatic CC. In this context, immunotherapy and immune checkpoint inhibitors (ICIs) are particularly likely to play a role in the treatment of cervical tumors in a variety of disease settings. Some promising immune checkpoints include programmed cell death 1 (PD-1), programmed death ligand 1 (PD-L1) and cytotoxic T lymphocyte antigen 4 (CTLA-4), which exert immunomodulatory effects as negative regulators of T-cell activation and suppress immune responses in cervical cancer through cancer cell immune evasion. Initial trials of ICIs for CC have shown encouraging results in terms of objective response rate (ORR), progression-free survival (PFS), and overall survival (OS), both monotherapy and combination strategies. Meanwhile, human papillomavirus, vaginal microecology and intestinal microenvironment play an important role in CC, which provides new treatment directions. This review analyzed a number of completed or ongoing clinical trials of ICIs in the treatment of advanced and recurrent/metastatic CC. And we also analyzed the important relationship between vaginal microecology and intestinal microecology with CC and their related immunotherapy prospects.

Genetics and beyond: Precision Medicine Real-World Data for Patients with Cervical, Vaginal or Vulvar Cancer in a Tertiary Cancer Center

“…This is consistent with the clinical observation of CC as an immune-related malignancy with a higher prevalence in immunocompromised patient cohorts [16]. It is also in line with the close relationship between CC oncogenesis and DNA repair defects (dMMR, HRD) leading to the emergence of potentially immunogenic tumor neoantigens [17]. In this context, the ESMO Next Generation Sequencing (NGS) Recommendations had advocated testing of tumor mutational burden (TMB) in cervical cancer patients as early as 2020 [18], given the clinical benefits of checkpoint blockade in patients with dMMR deficiency or high microsatellite instability (MSI-H) observed in the KEYNOTE-158 trial.…”

The role of TOP2A in immunotherapy and Vasculogenic mimicry in non-small cell lung cancer and its potential mechanism

“…In recent years, immune checkpoint inhibitors (ICIs) have been shown to be one of the most promising and effective immunotherapies, which reconstitute anti-tumor responses and prevent tumor cells from evading immune surveillance by targeting speci c molecules, such as programmed death receptor 1 (PD-1) or its ligand (PD-L1) and cytotoxic T-lymphocyte antigen 4 (CTLA-4) [52][53][54]. Our current ndings suggest that TOP2A is involved in regulating the expression of immune checkpoint (PD-L1) in NSCLC, and the upregulation of TOP2A signi cantly promotes the expression of immune checkpoint (PD-L1).…”

Current Methods and Advances in the Immunotherapy Treatment of Non-Ovarian Gynaecological Cancers

“…In addition to PD-1/PD-L1, the CTLA-4 immune checkpoint is also critical in the response to T-cell activation. ICIs targeting CTLA-4 have been a major focus of immunotherapy development in several malignancies, including CC, with ipilimumab being the most widely researched anti-CTLA-4 monoclonal antibody for CC [158]. In the clinical trials GOG-9929 (NCT01711515) [159] and 938TiPA (NCT01693783) [160], ipilimumab demonstrated immune-modulating activity in significant T-cell population expansion as an adjuvant therapy to definitive CRT in women with locally advanced CC [159] but no significant response as a monotherapy in metastatic CC [160].…”