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Review
. 2021 Oct 21;57(11):1141.
doi: 10.3390/medicina57111141.

The Role of Chemokines in Cervical Cancers

Fabian Garrido  1 , Carl Mathis Wild  1 , Johanna Mittelberger  1 , Franziska Dobler  1 , Mariella Schneider  1 , Nadine Ansorge  1 , Melitta Köpke  1 , Annamarie Strieder  1 , Nina Ditsch  1 , Udo Jeschke  1 , Christian Dannecker  1
Affiliations
Review

The Role of Chemokines in Cervical Cancers

Fabian Garrido et al. Medicina (Kaunas). .

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.

Keywords: CCL1-28; CX3CL1; CXCL1-17; PD-1; PD-L1; XCL1-2; immune checkpoints.

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Conflict of interest statement

N.D. reports funding by: MSD, Novartis, Pfizer, Roche, AstraZeneca, TEVA, Mentor, and MCI Healthcare. C.D. is funded by Roche, AstraZeneca, TEVA, Mentor, and MCI Healthcare. All other authors report no conflict of interests. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Summary of the described chemokines of the CC chemokine proteins (or β chemokine proteins) family. These chemokines have two adjacent cysteine (amino acids) near their amino terminus. Although at least 27 different member of this subgroup have been reported for mammals, referred to as CC chemokine ligands (CCL)-1 to -28, we focused in this review on 10 CCL chemokines and described ligand receptor interaction for CCL2, -3, -4, -5, -8, -20 and -22 specifically for their function in cervical cancer. Abbreviations: HPV—human papilloma virus; CCL—C-C Motif Chemokine Ligand; C-C chemokine receptor; E6—HPV E6 protein; E7—HPV E7 protein; OS—overall survival rate; TPCA-1-2-[(aminocarbonyl)amino]-5-(4-fluorophenyl)-3-thiophenecarboxamide; Treg—T regulatory cells.
Figure 2
Figure 2
Summary of the CXC-chemokines, its receptor binding partner and main function in cervical cancer. A total of six CXC-chemokines (CXCL-1, -2, -3, -5, -6, & -8 bind to the same receptor CXCR2. Abbreviations: CX-Ca—carcinoma of the uterine cervix; CXCL—C-X-C motif chemokine; CXCR—C-X-C motif receptor; AKIP1—A-Kinase Interacting Protein 1; OS—overall survival.
Figure 3
Figure 3
Systematic depiction of the booster E7 vaccination effect by simultaneous application of PD-L1 and SLC, and correlation between plasma cells, CD8+ T cells, and regulatory T cells and the CCR7 expression. Abbreviations: CCR—C-C motif receptor; CCL—C-C motif ligand; CXCL—C-X-C motif ligand; PD-L1 - programmed cell Death protein 1 ligand; E7—HPV E7 protein; IL—interleukin; VEGF—vascular endothelial growth factor; IFN—interferon; T8+—CD8+ T cells; SLC—secondary lymphoid tissue chemokine.
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