Immunogenic Cell Death-related Cancer-associated Fibroblast Clusters and Prognostic Risk Model in Cervical Cancer

Overview

Journal APL Bioeng

Date 2024 Dec 18

PMID 39691350

Authors

Fei Wu

Yue Xu

Affiliations

Soon will be listed here.

Abstract

Cervical cancer (CC) remains a leading cause of female cancer mortality globally. Immunogenic cell death (ICD) influences the tumor microenvironment (TME) and adaptive immune responses. Cancer-associated fibroblasts (CAFs) within the TME suppress anti-tumor immunity and contribute to CC progression. This study identified three ICD-related CAF clusters linked to patient survival, including IL6+CAF and ILR1+CAF, which were associated with clinical outcomes. Using a nine-gene risk model, patients were stratified into risk groups, with high-risk individuals showing worse survival and correlations with pathways such as hypoxia and TGFβ. The model also predicted immunotherapy responses, highlighting immune infiltration differences across risk groups. These findings provide insights into the role of CAF clusters in CC and present a risk model that supports prognosis prediction and personalized therapy.

References

Mariathasan S, Turley S, Nickles D, Castiglioni A, Yuen K, Wang Y . TGFβ attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells. Nature. 2018; 554(7693):544-548. PMC: 6028240. DOI: 10.1038/nature25501. View

Aran D, Looney A, Liu L, Wu E, Fong V, Hsu A . Reference-based analysis of lung single-cell sequencing reveals a transitional profibrotic macrophage. Nat Immunol. 2019; 20(2):163-172. PMC: 6340744. DOI: 10.1038/s41590-018-0276-y. View

Tilborghs S, Corthouts J, Verhoeven Y, Arias D, Rolfo C, Trinh X . The role of Nuclear Factor-kappa B signaling in human cervical cancer. Crit Rev Oncol Hematol. 2017; 120:141-150. DOI: 10.1016/j.critrevonc.2017.11.001. View

Sheng Y, Zhang B, Xing B, Liu Z, Chang Y, Wu G . Cancer-Associated Fibroblasts Exposed to High-Dose Ionizing Radiation Promote M2 Polarization of Macrophages, Which Induce Radiosensitivity in Cervical Cancer. Cancers (Basel). 2023; 15(5). PMC: 10001412. DOI: 10.3390/cancers15051620. View

Li C, Liu D, Yang S, Hua K . Integrated single-cell transcriptome analysis of the tumor ecosystems underlying cervical cancer metastasis. Front Immunol. 2022; 13:966291. PMC: 9780385. DOI: 10.3389/fimmu.2022.966291. View

Elia I, Rowe J, Johnson S, Joshi S, Notarangelo G, Kurmi K . Tumor cells dictate anti-tumor immune responses by altering pyruvate utilization and succinate signaling in CD8 T cells. Cell Metab. 2022; 34(8):1137-1150.e6. PMC: 9357162. DOI: 10.1016/j.cmet.2022.06.008. View

Qiang L, Hoffman M, Ali L, Castillo J, Kageler L, Temesgen A . Transforming Growth Factor-β Blockade in Pancreatic Cancer Enhances Sensitivity to Combination Chemotherapy. Gastroenterology. 2023; 165(4):874-890.e10. PMC: 10526623. DOI: 10.1053/j.gastro.2023.05.038. View

Liu P, Zhao L, Pol J, Levesque S, Petrazzuolo A, Pfirschke C . Crizotinib-induced immunogenic cell death in non-small cell lung cancer. Nat Commun. 2019; 10(1):1486. PMC: 6445096. DOI: 10.1038/s41467-019-09415-3. View

Huang D, Li C . circ-ACACA promotes proliferation, invasion, migration and glycolysis of cervical cancer cells by targeting the miR-582-5p/ERO1A signaling axis. Oncol Lett. 2021; 22(5):795. PMC: 8461755. DOI: 10.3892/ol.2021.13056. View

10.

Fernandes A, Viveros-Carreno D, Hoegl J, Avila M, Pareja R . Human papillomavirus-independent cervical cancer. Int J Gynecol Cancer. 2021; 32(1):1-7. DOI: 10.1136/ijgc-2021-003014. View

11.

Zhang Y, Zhao Y, Ran Y, Guo J, Cui H, Liu S . Alantolactone exhibits selective antitumor effects in HELA human cervical cancer cells by inhibiting cell migration and invasion, G2/M cell cycle arrest, mitochondrial mediated apoptosis and targeting Nf-kB signalling pathway. J BUON. 2020; 24(6):2310-2315. View

12.

Cai H, Yan L, Liu N, Xu M, Cai H . IFI16 promotes cervical cancer progression by upregulating PD-L1 in immunomicroenvironment through STING-TBK1-NF-kB pathway. Biomed Pharmacother. 2020; 123:109790. DOI: 10.1016/j.biopha.2019.109790. View

13.

Yuan Y, Cai X, Shen F, Ma F . HPV post-infection microenvironment and cervical cancer. Cancer Lett. 2020; 497:243-254. DOI: 10.1016/j.canlet.2020.10.034. View

14.

Moslehi J, Lichtman A, Sharpe A, Galluzzi L, Kitsis R . Immune checkpoint inhibitor-associated myocarditis: manifestations and mechanisms. J Clin Invest. 2021; 131(5). PMC: 7919710. DOI: 10.1172/JCI145186. View

15.

Liao Z, Tan Z, Zhu P, Tan N . Cancer-associated fibroblasts in tumor microenvironment - Accomplices in tumor malignancy. Cell Immunol. 2018; 343:103729. DOI: 10.1016/j.cellimm.2017.12.003. View

16.

Erez N, Truitt M, Olson P, Arron S, Hanahan D . Cancer-Associated Fibroblasts Are Activated in Incipient Neoplasia to Orchestrate Tumor-Promoting Inflammation in an NF-kappaB-Dependent Manner. Cancer Cell. 2010; 17(2):135-47. DOI: 10.1016/j.ccr.2009.12.041. View

17.

Zhou J, Wang G, Chen Y, Wang H, Hua Y, Cai Z . Immunogenic cell death in cancer therapy: Present and emerging inducers. J Cell Mol Med. 2019; 23(8):4854-4865. PMC: 6653385. DOI: 10.1111/jcmm.14356. View

18.

Moon H, Park W, Sung S, Choi E, Chung H, Woo B . Immunohistochemical and quantitative competitive PCR analyses of midkine and pleiotrophin expression in cervical cancer. Gynecol Oncol. 2003; 88(3):289-97. DOI: 10.1016/s0090-8258(02)00070-7. View

19.

Ma X, Zhang Y, Wang S, Wei H, Yu J . Immune checkpoint inhibitor (ICI) combination therapy compared to monotherapy in advanced solid cancer: A systematic review. J Cancer. 2021; 12(5):1318-1333. PMC: 7847663. DOI: 10.7150/jca.49174. View

20.

Yang R, Zhan Y, Li Y, Dai S, He S, Ye C . The Cellular and Molecular Landscape of Synchronous Pediatric Sialoblastoma and Hepatoblastoma. Front Oncol. 2022; 12:893206. PMC: 9289541. DOI: 10.3389/fonc.2022.893206. View