PD-1/PD-L1 inhibitors for advanced or metastatic cervical cancer: From bench to bed

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.

The potential of PCNA inhibition as a therapeutic strategy in cervical cancer

“…There are several strategies being employed as novel therapeutics, including immune checkpoint (PD-1 and PD-L1) inhibitors. 27 These drugs work by reinvigorating the immune response against the tumor. At least 17 clinical trials have investigated this class of drugs in CaCx, focusing on pembrolizumab, nivolumab, sintilimab, cemiplimab, and atezolizumab with or without other drugs.…”

“…There are several strategies being employed as novel therapeutics, including immune checkpoint (PD‐1 and PD‐L1) inhibitors 27 . These drugs work by reinvigorating the immune response against the tumor.…”

Tislelizumab for cervical cancer: A retrospective study and analysis of correlative blood biomarkers

“…In China, CC ranks as the second most frequently diagnosed cancer in women ( 3 ). Despite advances in vaccination, and screening, approximately 15% of patients are diagnosed with recurrent or metastatic (R/M) disease, with a 5-year survival rate of 15% ( 4 , 5 ). Platinum-based chemotherapy combined with the anti-angiogenesis agent bevacizumab is the first-line treatment for R/M CC; however, the antitumor response rate is low ( 2 , 6 ).…”

Meta-analysis of the efficacy and safety of Xihuang Pills/capsules in adjuvant treatment of uterine cervical neoplasms

“…[3] Non-surgical regimens have now become the prevailing approach for intermediate and advanced cervical cancer, encompassing radiotherapy, chemotherapy, targeted therapy, and immunotherapy as the most commonly employed modalities. [4] Radiotherapy and chemotherapy have gained clinical recognition as fundamental treatment methods, often administered in tandem. [5] Despite their relatively significant clinical effects, accumulating research suggests that these therapies are associated with numerous complications, toxicities, and side effects, [6] including myelosuppression, [7][8][9] gastrointestinal reactions, [10] radiation proctitis, and radiation cystitis.…”