Immune response and evasion mechanisms in lip carcinogenesis: An immunohistochemical study

Lopes, Maria Luiza Diniz de Sousa; Gonzaga, Amanda Katarinny Goes; Mosconi, Carla; Palomino, Gustavo Martelli; Mendonça, Elismauro Francisco; Batista, Aline Carvalho; Silveira, Éricka Janine Dantas da

doi:10.1016/j.archoralbio.2018.09.017

Cited by 12 publications

(22 citation statements)

References 43 publications

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“…The studies included in this systematic review involved patients with potentially malignant squamous lesions from Asia, [25][26][27][28][29][30][31][32] Europe, 33,34 South America, 35,36 and North America. 37,38 Two of the included studies were represented by abstracts only.…”

Section: Characteristics Of Included Studiesmentioning

confidence: 99%

“…37,38 The type of premalignant lesions in studies varied: eight studies dealt with oral dysplasia lesions, [27][28][29][30][31][32][33]38 three studies considered oral leukoplakia with or without dysplasia, 25,34,35 two studies used the broad terminology of "oral epithelial premalignant lesion," 26,37 and one focused on actinic cheilitis. 36 The prevalence of PD-L1 expression was one of the main aims of the study in nine publications, 25,26,30,[33][34][35][36][37][38] while in the remaining studies the main outcome was the expression of other markers of the immunological microenvironment and their correlation with PD-L1 among other molecules. Summary information on the included studies is found in Table 1.…”

Section: Characteristics Of Included Studiesmentioning

confidence: 99%

“…Pooling data from nine studies, 25,26,30,[33][34][35][36][37][38] the pooled prevalence of PD-L1 positivity in precancerous lesions of the head and neck was 48.25% (CI 21.07-75.98) with high heterogeneity (I 2 98%, tau2 0.1797, P < .01; Figure 2). The pooled prevalence of PD-L1 positivity was recalculated after removal of an outlier study (the study by Gonçalves et al 35 ) which was individuated with the assessment of studentized residuals, but high heterogeneity remained (pooled estimate 38.34%, CI 19.17-59.48, I 2 95%, tau2 0.0822, P < .01).…”

Section: Prevalence Of Pd-l1 In Precancerous Lesions and Subgroup Amentioning

confidence: 99%

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Prevalence of PD‐L1 expression in head and neck squamous precancerous lesions: a systematic review and meta‐analysis

Girolami¹,

Pantanowitz

Munari

et al. 2020

Head & Neck

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Background Studies concerning programmed death‐ligand 1 (PD‐L1) expression in precancerous lesions of head and neck (HN) region have shown variable results. Methods We systematically reviewed the published evidence on PD‐L1 expression in HN precancerous lesions. Results Of 1058 original articles, 14 were included in systematic review and 9 in meta‐analysis. The pooled estimate of PD‐L1 expression was 48.25% (confidence interval [CI] 21.07‐75.98, I2 98%, tau2 0.18). PD‐L1 expression appeared to be more frequent in precancerous lesions than in normal mucosa (risk ratio [RR] 1.65, CI 0.65‐4.03, I2 91%, tau2 0.82) and less frequent than in invasive squamous cell carcinoma (RR 0.68, CI 0.43‐1.08, I2 91%, tau2 0.22). Conclusions PD‐L1 expression could reflect a point of balance between host immune response and cancer escape ability. High heterogeneity and moderate quality suggest that further studies with larger sample size and more rigorous case selection will allow more precise assessment of PD‐L1 expression in HN precancerous lesions.

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Section: Characteristics Of Included Studiesmentioning

confidence: 99%

Section: Characteristics Of Included Studiesmentioning

confidence: 99%

Section: Prevalence Of Pd-l1 In Precancerous Lesions and Subgroup Amentioning

confidence: 99%

See 1 more Smart Citation

Prevalence of PD‐L1 expression in head and neck squamous precancerous lesions: a systematic review and meta‐analysis

Girolami¹,

Pantanowitz

Munari

et al. 2020

Head & Neck

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“…Anti-PD1 (prembolizumab and nivolumab), anti-PD-L1 (atezolizumab, durvalumab, and avelumab), and anti-CTLA4 (ipilimumab) therapies have been introduced to treat multiple kinds of cancer. However, while having provided substantial promise as a new treatment strategy, the modulation by immune checkpoint therapies are only successful in 15–20% of patients [241,242,243,244,245,246]. One reason for this limited activity of checkpoint inhibitors might be the simultaneous expression of embryonic HLA genes on cancer cells, which govern an independent immune inhibition mechanism.…”

Section: Significance For Immunoncologymentioning

confidence: 99%

“…Similarly, Lopes et al observed coexpression of PD-L1 and HLA-G proteins in lip carcinomas. This coexpression was associated with a higher malignancy and occurrence of systemic metastases [246]. Therefore, it is conceivable that, when confronted with protective mechanisms similar to the defense mechanisms in pregnancy, immune oncological therapeutic approaches are less effective than expected [248].…”

Section: Significance For Immunoncologymentioning

confidence: 99%

European Patent in Immunoncology: From Immunological Principles of Implantation to Cancer Treatment

Würfel¹,

Winterhalter²,

Trenkwalder³

et al. 2019

IJMS

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The granted European patent EP 2 561 890 describes a procedure for an immunological treatment of cancer. It is based on the principles of the HLA-supported communication of implantation and pregnancy. These principles ensure that the embryo is not rejected by the mother. In pregnancy, the placenta, more specifically the trophoblast, creates an “interface” between the embryo/fetus and the maternal immune system. Trophoblasts do not express the “original” HLA identification of the embryo/fetus (HLA-A to -DQ), but instead show the non-classical HLA groups E, F, and G. During interaction with specific receptors of NK cells (e.g., killer-immunoglobulin-like receptors (KIR)) and lymphocytes (lymphocyte-immunoglobulin-like receptors (LIL-R)), the non-classical HLA groups inhibit these immunocompetent cells outside pregnancy. However, tumors are known to be able to express these non-classical HLA groups and thus make use of an immuno-communication as in pregnancies. If this occurs, the prognosis usually worsens. This patent describes, in a first step, the profiling of the non-classical HLA groups in primary tumor tissue as well as metastases and recurrent tumors. The second step comprises tailored antibody therapies, which is the subject of this patent. In this review, we analyze the underlying mechanisms and describe the currently known differences between HLA-supported communication of implantation and that of tumors.

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Topical Delivery of Nivolumab, a Therapeutic Antibody, by Fractional Laser and Pneumatic Injection

et al. 2020

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Background and Objectives PD‐L1 is a tumor ligand that binds to the PD‐1 receptor on immune cells, thereby inhibiting the antitumor immune response. The antibody nivolumab is a PD‐1 inhibitor, Food and Drug Administration approved for systemic treatment of several aggressive cancer types. Topically applied nivolumab may hold potential as a future strategy to treat keratinocyte cancer, but its molecular properties preclude unassisted topical uptake. The aim of this study was to investigate uptake and biodistribution of topically delivered nivolumab, assisted by two physical enhancement techniques with different delivery kinetics; ablative fractional laser (AFL) and electronically controlled pneumatic injection (EPI). Study Design/Materials and Methods In vitro porcine skin was exposed to CO2 AFL (20 mJ/mb, 5% density), followed by passive diffusion of nivolumab in a Franz cell (1 mg/ml, 18 hours, n = 6) or treated with EPI (4 bar) for immediate delivery of nivolumab (1 mg/ml, 10 minutes, n = 6). The resulting nivolumab skin concentrations were quantified by enzyme‐linked immunosorbent assay (ELISA) at three skin depths (100, 500, and 1500 µm), comparing the uptake from assisted delivery with intact skin. Biodistribution of nivolumab in the skin for all interventions was visualized by laser ablation‐inductively coupled plasma‐mass spectrometry (LA‐ICP‐MS) and fluorescence microscopy. Results Delivery of nivolumab by AFL‐assisted passive diffusion and immediate EPI both resulted in significantly enhanced uptake of nivolumab in all skin depths compared with intact skin (P < 0.05). With AFL, nivolumab concentrations reached 86.3 µg/cm3 (100 µm), 105.8 µg/cm3 (500 µm), and 19.3 µg/cm3 (1500 µm), corresponding to 2–10% of the applied concentration, with the highest deposition in the mid dermis. Immediate EPI delivered 429.4 µg/cm3 (100 µm), 584.9 µg/cm3 (500 µm), and 295.9 µg/cm3 (1500 µm) into the skin, corresponding to 29–58% of the applied nivolumab concentration. From qualitative visualization of the biodistribution, it appeared that nivolumab distributed in a horizontal and continuous homogenous band in the upper and mid dermis through AFL‐exposed skin, whereas EPI‐delivery showed a deep focal deposition extending into the deep dermis. Conclusions AFL‐assisted passive diffusion and immediate EPI‐assisted delivery show the potential to deliver therapeutic antibodies locally. Future in vivo and pharmacokinetic studies would reveal the full potential for topical antibody delivery by energy‐based devices. Lasers Surg. Med. © 2020 Wiley Periodicals LLC

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Immune response and evasion mechanisms in lip carcinogenesis: An immunohistochemical study

Cited by 12 publications

References 43 publications

Prevalence of PD‐L1 expression in head and neck squamous precancerous lesions: a systematic review and meta‐analysis

Prevalence of PD‐L1 expression in head and neck squamous precancerous lesions: a systematic review and meta‐analysis

European Patent in Immunoncology: From Immunological Principles of Implantation to Cancer Treatment

Topical Delivery of Nivolumab, a Therapeutic Antibody, by Fractional Laser and Pneumatic Injection

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