Immunotherapy Treatment Against Cervical Cancer

Abstract

Cervical cancer (CC) is one of the most common gynecological tumors and an important health problem, especially in developing countries. The vast majority of patients in early stages are cured of the disease with surgical treatment and with concomitant chemoradiotherapy in locally advanced stages. However, in patients with recurrent, persistent, or metastatic cervical CC, the effectiveness of treatment is limited, except for the combination of chemotherapy based on platinum doublets plus bevacizumab, the treatment that has achieved the best results to date. Programmed cell death-1/PD ligand-1 (PD-1/PD-L1) inhibitors could be a novel and cutting-edge therapeutic option to improve clinical outcomes in this group of patients. Thus far, there are a few Phase I/II clinical trials that have assessed the usefulness of pembrolizumab and nivolumab in this group of patients; these include the KEYNOTE 028, KEYNOTE 158, and CHECKMATE 358 trials, in which clinical benefit has been proven with PD-1/PD-L1 inhibitors in recurrent, persistent, or metastatic CC, as second-line treatment. There are also some ongoing trials that could provide further evidence on the PD-1/PD-L1 pathway as a therapeutic target in CC. In this review, we will focus on the usefulness of these PD-1/PDL1 inhibitors in CC, as well as on trials that are still in the recruitment phase, to confirm their effectiveness in this clinical setting.

Signature of seven cuproptosis-related lncRNAs as a novel biomarker to predict prognosis and therapeutic response in cervical cancer

“…Combination therapy with ICIs can overcome tumor resistance and improve treatment outcomes ( Patel and Minn, 2018 ; Zhang et al, 2022 ). It has now been shown that inhibitors of PD-1 and CTLA4 can harness the host immune system to achieve antitumor effects in the treatment of CC ( Jiménez-Lima et al, 2020 ; Wendel Naumann and Leath, 2020 ). Therefore, identifying patients who are candidates for ICI therapy in clinical practice is critical.…”

Monoclonal antibodies in cervical malignancy-related HPV

“…Long-term use of durvalumab has also been reported to cause side effects such as pneumonitis, hepatitis, colitis or diarrhea, hypothyroidism, adrenal insufficiency, hypophysitis or hypopituitarism, type 1 diabetes, nephritis, and skin rash or dermatitis. Other side effects such as diarrhea, fatigue, and hypokalemia were observed in 35%, 25%, and 25% of cases, respectively ( 13 ).…”

“…Durvalumab (ImfinziTM; AstraZeneca) is a human monoclonal antibody that suppresses PD-L1, prevents it from interacting with PD-1, and increases the cytotoxic and anti-tumor activity of T cells ( 13 ). This antibody was approved by the FDA on May 1, 2017, due to its ORR in treating local metastatic or advanced urothelial cancer ( 85 ).…”

“…Atezolizumab, as an IgG1 subclass human monoclonal antibody, leads to increased activity of cytotoxic T cells and tumor-infiltrating lymphocytes and also interacts with the PD-L1 ligand ( 13 ). On the other hand, this antibody inhibits PD-L1 and PD-1 interaction, which disrupts the activity of the cellular immune system and T lymphocytes ( 87 ).…”

“…PD-L1 is not expressed in normal cervical cells and benign cervical lesions ( 10 – 12 ). Moreover, immunomodulatory therapies such as PD-1/PD-L1 inhibitors, CTLA-4, 4-1BB, and other cellular pathways including vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) are studied in clinical trials ( 13 ) (Monoclonal antibodies related to each of the mentioned items are listed as a table in a Supplementary File ). Despite the improvements in our understanding of HPV infection and subsequent cervical cancer processes, no particular therapy has been recommended in clinical trials yet ( 14 – 16 ).…”