Leukoplakia and Immunology: New Chemoprevention Landscapes?
Abstract
:1. Introduction
2. Oral Leukoplakia: Immunopathology and Rationale for the Use of Immunotherapies
3. Immunopathology and Field Cancerization
4. Mutational Load and Immunology: Should These Factors Be Analyzed in Chemoprevention Studies?
5. Immunology and Aging in Patient Affected by Oral Precancerous Lesion: Does a Progressive Increase in Mutational Load and Immunosenescence Concern Us?
6. Chemoprevention of Oral Leukoplakia: Basic Concepts
7. Immunoprevention: Possible Role of Vaccination in Preventing Preneoplastic Oral Lesions
8. Immunotherapy: Can the Modulation of the Immune Response through the Use of Drugs Help in the Prevention of Preneoplastic Lesions?
9. Discussion and Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Definition | Principal Target | Date | Ref. |
---|---|---|---|
Chemoprevention is the use of synthetic or natural compounds for the reversal, suppression, or prevention of a premalignant lesion conversion to an invasive form. | Therapy of intraepithelial neoplasia | 1976 | [7] |
Biochemoprevention | Combined use of interferon, 13-cis retinoic acid and alpha tocopherol | 1999 | [9] |
Short-term intermittent therapy to eliminate premalignancy (SITEP). | Intermittent dosing schedules:
| 2011 | [10] |
Molecular prevention: the use of natural or synthetic agents that interrupt the prime drivers, key derangements or the context in which these drivers act and in which the derangements occur, prior to invasion across the basement membrane | Genetic, epigenetic. | 2015 | [11] |
Green chemoprevention as a modern approach to highlight healthy lifestyle changes that aim to decrease the incidence of head and neck cancer. | Typically, is believed to act through epigenetic influence. | 2018 | [8,12] |
Type of Drug | Route of Administration In Vivo | Type of Study | Target in the Study | Major Results | Ref. |
---|---|---|---|---|---|
HPV vaccine | Parental | Clinical | High risk HPV | Efficacy not proven for oral preneoplastic lesion prevention | [31,32] |
Dendritic cell vaccine | Parental | Experimental | Potentially malignant disorder-pulsed dendritic cell | Induction of immune reactivity | [33] |
Dendritic cell vaccine | Parental | Experimental | (A) Potentially malignant disorder-pulsed dendritic cell vaccine; (B) Normal tongue epithelium lysate-pulsed dendritic cells vaccine | Reduction of lesion burden at 8 weeks; Rapid increase (B) or delayed increase (A) in stimulatory immune effectors | [34] |
Cyclic dinucleotides | Parental | Experimental | Stimulation of interferon genes (STING) | Vaccine adjuvant; promoting both T cell and humoral responses. | [35] |
Cyclic dinucleotides | Parental | Experimental | Stimulation of interferon genes (STING); interestingly STING could be found in the basal layer of normal tonsil and in tonsillar crypts. | Regression of papilloma. Immuno-prevention of cancer and precancer HPV+ | [36] |
Alfa interferon | Parental | Combinational chemoprevention trial. Combined use with 13-cis retinoic acid and alpha tocopherol | Stimulates the production of enzymes modulating the immune response | Moderate effectiveness for laryngeal dysplasia. Poor response oral lesions | [9] |
(A) Tocilizumab (B) Reparixin |
| Experimental, combination treatment with Fenretinide, tocilizumab and Reparixin in vitro. | (A) Humanized monoclonal antibody against the interleukin-6 receptor. (B) Inhibitor of the chemokine receptors CXCR1 and CXCR2 | Treatment significantly suppressed IL-6 and IL-8 release, stem cell gene expression, and invasion | [37] |
Pembrolizumab | Parental | Randomized phase II trial study. Start Date: 14 June 2017 Estimated Primary Completion Date: 1 March 2024 | Humanized antibody. Programmed cell death protein 1 (PD-1) receptor. | Results not available | [38] |
Tacrolimus | Topical | Experimental | Calcineurin inhibitors with blocking the production and release of pro-inflammatory cytokines in T cells, and improving the barrier function of the skin and the mucosa | No reduction of factors related to malignant transformation unchanged | [39] |
Sirolimus | Topical | Clinical | m-TOR inhibitor 5 mL of a 1 mg/mL solution of sirolimus twice a day as a rinse | local anti-inflammatory effects | [40] |
Dietary supplementation with vitamin A, treatment with agonists, or inhibitors of retinoic acid receptors | Systemic | Experimental-Clinical | Natural and vaccine-induced immunity against infections or cancer. Modulation of retinoic acid signaling | Modulation of immune activity | [41] |
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Grigolato, R.; Bizzoca, M.E.; Calabrese, L.; Leuci, S.; Mignogna, M.D.; Lo Muzio, L. Leukoplakia and Immunology: New Chemoprevention Landscapes? Int. J. Mol. Sci. 2020, 21, 6874. https://doi.org/10.3390/ijms21186874
Grigolato R, Bizzoca ME, Calabrese L, Leuci S, Mignogna MD, Lo Muzio L. Leukoplakia and Immunology: New Chemoprevention Landscapes? International Journal of Molecular Sciences. 2020; 21(18):6874. https://doi.org/10.3390/ijms21186874
Chicago/Turabian StyleGrigolato, Roberto, Maria Eleonora Bizzoca, Luca Calabrese, Stefania Leuci, Michele Davide Mignogna, and Lorenzo Lo Muzio. 2020. "Leukoplakia and Immunology: New Chemoprevention Landscapes?" International Journal of Molecular Sciences 21, no. 18: 6874. https://doi.org/10.3390/ijms21186874