Abstract
Both clinical-pathological and experimental studies have shown that chemokines play a key role in activating the immune checkpoint modulator in cervical cancer progression and are associated with prognosis in tumor cell proliferation, invasion, angiogenesis, chemoresistance, and immunosuppression. Therefore, a clear understanding of chemokines and immune checkpoint modulators is essential for the treatment of this disease. This review discusses the origins and categories of chemokines and the mechanisms that are responsible for activating immune checkpoints in cervical dysplasia and cancer, chemokines as biomarkers, and therapy development that targets immune checkpoints in cervical cancer research.
Highlights
With around 565,000 new cases per year, cervical cancer (CC) is the second most frequent female cancer and the third leading cause for cancer death in female patients worldwide [1,2]
A histopathologic study showed that the expression of CCL2 and CCL19 were inversely associated with the expression of atypical chemokine receptors (ACRs), including CCX-CKR, DARC, and D6, which have been reported to be involved in cancer invasion and metastasis in patients with cervical squamous cell carcinoma [32]
These results show that an increased CCL17 expression in cervical lesions is a significant inducer of the proliferation of squamous cells and adenocarcinoma of the cervix via the Jun N-terminal kinase (JNK) and STAT5 pathways [8]
Summary
With around 565,000 new cases per year, cervical cancer (CC) is the second most frequent female cancer and the third leading cause for cancer death in female patients worldwide [1,2]. Chemokines, a subgroup of cytokines, are defined as signaling molecules which are responsible for chemotaxis. According to their spacing of the two conserved N-terminal cysteines they are subdivided into four groups: CXC, CC, CX3C, and C. Chemokine (C-motif) ligands (XCL1 and -2) are small cytokines from the family of C chemokines, known as lymphotactin. XCL1 is closely related to XCL2, whose gene localization can be found on chromosome 1. Both have many genetic and functional similarities; XCL2 has so far only been described in the human system. CX3CL1 plays a role in the recruitment of cytotoxic cells and in the elimination of cells that may undergo malignant transformation [15,16,17,18,19,20,21,22,23]
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