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PD-1/PD-L1 inhibitors for advanced or metastatic cervical cancer: From bench to bed
Weijia Huang1,2, Jiewei Liu1, Kai Xu1,2
1Lung Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
Abstract:
Advanced or metastatic cervical cancer has a poor prognosis, and the 5-year overall survival is <5% with conventional radiotherapy and chemotherapy. Immunotherapy, particularly immune checkpoint inhibitors (ICIs), achieved initial success in advanced solid tumors, while their efficacy and safety in advanced or metastatic cervical cancer remains to be explored. Previous studies found high-risk HPV infection and elevated PD-L1 expression in cervical precancerous lesions and squamous cell carcinoma. Meanwhile, elevated PD-L1 expression, high cytotoxic T lymphocyte infiltration, and abnormal cytotoxic T lymphocyte function might benefit inflammation infiltration for ICIs in the tumor microenvironment. Patients with HPV infection, squamous cell carcinoma, advanced stage, large tumor size, poor differentiation, metastatic disease, history of multiple childbirth and abortion, or a previous history of receiving chemotherapy might be associated with positive PD-L1 expression. Although there is no correlation between PD-L1 expression and prognosis using conventional radiotherapy, patients with high PD-L1 expression have a poorer prognosis. Several clinical studies demonstrate preliminary safety and efficacy for PD-1/PD-L1 inhibitors, and the exploration of combination strategies such as immunotherapy combined with chemotherapy, radiotherapy, anti-angiogenesis therapy, or dual ICIs is ongoing. This paper systematically reviews PD-L1 expression patterns and their relationship with prognosis, along with reported and ongoing clinical trials of PD-1/PD-L1 inhibitors in cervical cancer to clarify the prospect of ICIs for cervical cancer from bench to bed.
Insights
Immune checkpoint inhibitors show promise for advanced cervical cancer, a disease with poor survival rates. Research is exploring PD-L1 expression and combination therapies to improve outcomes.
Area of Science:
- Oncology
- Immunology
- Gynecologic Oncology
Background:
- Advanced or metastatic cervical cancer carries a poor prognosis with conventional treatments.
- Immune checkpoint inhibitors (ICIs) have shown success in other solid tumors.
- PD-L1 expression is noted in cervical cancer, potentially influencing immunotherapy response.
Purpose of the Study:
- To review PD-L1 expression patterns in cervical cancer.
- To analyze the relationship between PD-L1 expression and prognosis.
- To summarize clinical trials of PD-1/PD-L1 inhibitors in cervical cancer.
Main Methods:
- Systematic review of literature on PD-L1 expression in cervical cancer.
- Analysis of existing studies on PD-1/PD-L1 inhibitors.
- Review of ongoing clinical trials for immunotherapy in cervical cancer.
Main Results:
- Elevated PD-L1 expression is associated with factors like HPV infection and advanced stage.
- While not correlated with conventional radiotherapy prognosis, high PD-L1 expression indicates a poorer prognosis.
- Preliminary clinical studies show safety and efficacy for PD-1/PD-L1 inhibitors.
Conclusions:
- ICIs represent a promising therapeutic avenue for advanced cervical cancer.
- Combination strategies (chemotherapy, radiotherapy, anti-angiogenesis, dual ICIs) are under investigation.
- Further research is crucial to optimize ICI therapy for cervical cancer patients.
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