PD-L1 upregulation and tumour progression in conjunction with lncRNA UCA1 about oral squamous cell carcinoma. A systematic review.

Dr. Karthik  Shunmugavelu; Dr . Kavitha K; Dr. Evangeline Cynthia  Dhinakaran

doi:10.51168/sjhrafrica.v6i12.2200

Authors

Dr. Karthik Shunmugavelu BDS, MDS OMFP, MSC London, Mfdsrcs England, Mfdsrcps Glasgow, Faculty Affiliate Rcs Ireland, Affiliate Rcs Edinburgh, Mcip, Fibms, Usa, Masid Australia, Assistant Professor, Department of Dentistry, PSP Medical College Hospital and Research Institute, Tambaram, Kanchipuram main road, Oragadam, Panruti Kanchipuram district, Tamilnadu 631604 India.
Dr . Kavitha K MDS, Senior Resident, Govt Vellore Medical College &Hospital, India
Dr. Evangeline Cynthia Dhinakaran MBBS MD PATHOLOGY Assistant Professor Department of Pathology Sree Balaji Medical College and Hospital, Chrompet, Chennai-600044, Tamilnadu, India

DOI:

https://doi.org/10.51168/sjhrafrica.v6i12.2200

Keywords:

Long non-coding RNA, Oral squamous cell carcinoma, Long non-coding RNA; Oral squamous cell carcinoma; cancer-associated fibroblasts; tumor margins; tumor microenvironment; angiogenesis; cell–cell interaction; histone methylation; tumour microenvironment., tumor margins, tumor microenvironment, angiogenesis, cell–cell interaction, histone methylation, tumour microenvironment

Abstract

Background:

Oral squamous cell carcinoma (OSCC) remains a lethal malignancy with a poor prognosis, particularly in advanced stages. The tumour microenvironment (TME), rich in cancer-associated fibroblasts (CAFs) and immune checkpoint molecules like PD-L1, is critical in OSCC progression. This review investigates the specific role of long non-coding RNA UCA1 in orchestrating PD-L1 upregulation and tumour progression within the OSCC TME.

Methodology:

This systematic review followed PRISMA guidelines. A comprehensive search of five electronic databases (PubMed, Scopus, Web of Science, Embase, and Lilacs) was conducted from 2020 to 2024. The search strategy used Boolean operators with terms related to "Oral cancer," "long non-coding RNA," "UCA1," "cancer-associated fibroblasts," and "PD-L1." Four original research articles meeting the inclusion criteria were selected for final analysis.

Results:

The included studies demonstrate that LncRNA UCA1 influences OSCC prognosis through genetic variants. Furthermore, CAFs, whose prevalence increases with tumour grade, contribute to an immunosuppressive TME. Key mechanisms identified include CAF-derived extracellular vesicles promoting epithelial-mesenchymal transition and collagen crosslinking, and stromal enzymes like NNMT regulating angiogenesis. Crucially, these CAF-driven processes are implicated in the upregulation of PD-L1, facilitating immune evasion.

Conclusion:

LncRNA UCA1 and CAFs are pivotal in driving OSCC progression and immune evasion via PD-L1 upregulation. Their interplay creates a pro-tumorigenic and immunosuppressive niche that supports disease advancement and resistance.

Recommendation:

Future research should prioritize elucidating the precise molecular cascade linking UCA1, CAF activation, and PD-L1 expression. Targeting this axis holds significant promise for developing novel diagnostic biomarkers and combination immunotherapies for OSCC.

References

Mattick JS, Amaral PP, Carninci P, Carpenter S, Chang HY, Chen LL, et al. Long non-coding RNAs: definitions, functions, challenges, and recommendations. Nat Rev Mol Cell Biol. 2023;24(6):430-47. https://doi.org/10.1038/s41580-022-00566-8

Statello L, Guo CJ, Chen LL, Huarte M. Gene regulation by long non-coding RNAs and its biological functions. Nat Rev Mol Cell Biol. 2021;22(2):96-118. https://doi.org/10.1038/s41580-021-00330-4 https://doi.org/10.1038/s41580-020-00315-9

Johnson DE, Burtness B, Leemans CR, Lui VW, Bauman JE, Grandis JR. Head and neck squamous cell carcinoma. Nat Rev Dis Primers. 2020;6(1):92. https://doi.org/10.1038/s41572-020-00224-3

Warnakulasuriya S, Kerr AR. Oral Cancer Screening: Past, Present, and Future. J Dent Res. 2021;100(13):1423-1430. https://doi.org/10.1177/00220345211014795

Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209-49. https://doi.org/10.3322/caac.21660

Dahariya S, Paddibhatla I, Kumar S, Raghuwanshi S, Pallepati A, Gutti RK. Long non-coding RNA: Classification, biogenesis, and functions in blood cells. Mol Immunol. 2019;112:82-92. https://doi.org/10.1016/j.molimm.2019.04.011

Zhang XZ, Liu H, Chen SR. Mechanisms of long non-coding RNAs in cancers and their dynamic regulations. Cancers (Basel). 2020;12(5):1245. https://doi.org/10.3390/cancers12051245

Maruse Y, Kawano S, Jinno T, Matsubara R, Goto Y, Kaneko N, et al. Significant association of increased PD-L1 and PD-1 expression with nodal metastasis and a poor prognosis in oral squamous cell carcinoma. Int J Oral Maxillofac Surg. 2018;47(7):836-45. https://doi.org/10.1016/j.ijom.2018.01.004

Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012;12(4):252-64. https://doi.org/10.1038/nrc3239

Quail DF, Joyce JA. Microenvironmental regulation of tumor progression and metastasis. Nat Med. 2013;19(11):1423-37. https://doi.org/10.1038/nm.3394

Arunkumar G, Deva Magendhra Rao AK, Manikandan M, Arun K, Vinothkumar V, Revathidevi S, et al. Expression profiling of long non-coding RNA identifies linc-RoR as a prognostic biomarker in oral cancer. Tumour Biol. 2017;39(4):1010428317698366. https://doi.org/10.1177/1010428317698366

Xu Y, Jiang E, Shao Z, Shang Z. Long noncoding RNAs in the metastasis of oral squamous cell carcinoma. Front Oncol. 2021;10:616717. https://doi.org/10.3389/fonc.2020.616717

Chandra Gupta S, Nandan Tripathi Y. Potential of long non‐coding RNAs in cancer patients: from biomarkers to therapeutic targets. Int J Cancer. 2017;140(9):1955-67. https://doi.org/10.1002/ijc.30546

Fang Z, Zhang S, Wang Y, Shen S, Wang F, Hao Y, et al. Long non-coding RNA MALAT-1 modulates the metastatic potential of tongue squamous cell carcinomas partially through the regulation of small proline-rich proteins. BMC Cancer. 2016;16(1):706. https://doi.org/10.1186/s12885-016-2735-x

Erez N, Truitt M, Olson P, Hanahan D. Cancer-associated fibroblasts are activated in incipient neoplasia to orchestrate tumor-promoting inflammation in an NF-κB-dependent manner. Cancer Cell. 2010;17(2):135-47. https://doi.org/10.1016/j.ccr.2009.12.041

Del Vecchio F, Lee GH, Hawezi J, Bhome R, Pugh S, Sayan E, et al. Long non-coding RNAs within the tumour microenvironment and their role in tumour-stroma cross-talk. Cancer Lett. 2018;421:94-102. https://doi.org/10.1016/j.canlet.2018.02.022

Ringuette Goulet C, Bernard G, Tremblay S, Chabaud S, Bolduc S, Pouliot F. Exosomes induce fibroblast differentiation into cancer-associated fibroblasts through TGFβ signaling. Mol Cancer Res. 2018;16(7):1196-204. https://doi.org/10.1158/1541-7786.MCR-17-0784

Jiang W, Pan S, Chen X, Wang ZW, Zhu X. The role of lncRNAs and circRNAs in the PD-1/PD-L1 pathway in cancer immunotherapy. Mol Cancer. 2021;20(1):116. https://doi.org/10.1186/s12943-021-01406-7

Chen DS, Irving BA, Hodi FS. Molecular pathways: next-generation immunotherapy---inhibiting programmed death-ligand 1 and programmed death-1. Clin Cancer Res. 2012;18(24):6580-7. https://doi.org/10.1158/1078-0432.CCR-12-1362

Gajewski TF, Schreiber H, Fu YX. Innate and adaptive immune cells in the tumor microenvironment. Nat Immunol. 2013;14(10):1014-22. https://doi.org/10.1038/ni.2703

Greeshma LR, Joseph AP, Sivakumar TT, Raghavan Pillai V, Vijayakumar G. Correlation of PD-1 and PD-L1 expression in oral leukoplakia and oral squamous cell carcinoma: an immunohistochemical study. Sci Rep. 2023;13(1):21698. https://doi.org/10.1038/s41598-023-48572-w