Advances in immunotherapy for cervical cancer: recent developments and future directions

Abstract

There is an unmet need for novel therapies to improve clinical outcomes for patients with locally advanced, recurrent, or metastatic cervical cancer. Most cases of cervical cancer are driven by infection with human papillomavirus (HPV), which uses multiple mechanisms to avoid immune surveillance. Several classes of agents have been developed that seek to activate the immune system in order to overcome this resistance and improve treatment outcomes. These include immune checkpoint inhibitors, therapeutic vaccines, engineered T cells, and antibody-drug conjugates. Here, we review the immune landscape of cervical cancer and the growing clinical data regarding the use of immunotherapy. Checkpoint inhibitors are the best studied treatments, with encouraging phase II studies available in the definitive setting and recently published phase III data defining a new standard of care for patients with recurrent or metastatic disease. Vaccines and engineered T cells are generally in earlier phases of development but use unique mechanisms of immune activation. It is possible that combination of immunotherapy, with either conventional systemic therapy or multiple immunomodulatory agents, may provide further benefit. We also discuss possible synergies between immunotherapy and radiation therapy, which is frequently used in the management of cervical cancer. Ultimately, immunotherapy represents an emerging treatment option for patients with cervical cancer. It is an appropriate component of first-line treatment in the recurrent or metastatic setting and may soon be incorporated into definitive management of locally advanced disease.

Dissecting the Single-Cell Transcriptome Network of Immune Environment Underlying Cervical Premalignant Lesion, Cervical Cancer and Metastatic Lymph Nodes

“…Thus, therapies targeting the transformation of macrophage may be effect to inhibit lesion from HSIL to tumor. Immunotherapy with immune checkpoint inhibitors (ICIs) has changed the treatment paradigm for various cancer types and improved outcomes for patients with advanced or metastatic cancer (54). In this study, we found that some CD8 T cells expressed high levels of immune checkpoint genes in tumor or metastatic lymph node, such as PD-1, PD-L1 and CTLA4, suggesting that ICIs can be effective for CC treatment.…”

Integrated in silico analysis of LRP2 mutations to immunotherapy efficacy in pan-cancer cohort

“…Several tumor-specific genes have been reported as markers for predicting the benefit of ICIs. These markers are still insufficient to determine when and how often ICIs should be used [42]. In this study, we identified LRP2 mutations as a novel biomarker that predicated immunotherapy response.…”

O-Glycosylating Enzyme GALNT2 Predicts Worse Prognosis in Cervical Cancer

“…The staining extent was scored as <10% (0), 10%-25% (1), 25%-50% (2), 50%-75% (3), and >75% (4). The staining intensity was divided into four score ranks: no staining (0), light brown (1), brown (2), and dark brown (3).…”

“…Recently, immunotherapy has received extensive attention in the treatment of cervical cancer. However, the efficacy of antitumor immunotherapy in recurrent and advanced cervical cancer remains to be improved [ 3 ]. Therefore, it is urgent to find out key immune-related biomarkers of cervical cancer and reveal their potential mechanisms in the occurrence and development of cervical cancer.…”