scholarly journals Anticancer Effects of Sublingual Type I IFN in Combination with Chemotherapy in Implantable and Spontaneous Tumor Models

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 845
Author(s):  
Maria Ciccolella ◽  
Sara Andreone ◽  
Jacopo Mancini ◽  
Paola Sestili ◽  
Donatella Negri ◽  
...  
Keyword(s):  
Salivary Gland ◽  
Biological Effects ◽  
Salivary Gland Tumors ◽  
Sublingual Administration ◽  
Type I ◽  
Type I Ifn ◽  
Tumor Models ◽  
Antitumor Effects ◽  
Duct Carcinoma ◽  
Administration Routes

Salivary gland tumors are a heterogeneous group of neoplasms representing less than 10% of all head and neck tumors. Among salivary gland tumors, salivary duct carcinoma (SDC) is a rare, but highly aggressive malignant tumor resembling ductal breast carcinoma. Sublingual treatments are promising for SDC due to the induction of both local and systemic biological effects and to reduced systemic toxicity compared to other administration routes. In the present study, we first established that the sublingual administration of type I IFN (IFN-I) is safe and feasible, and exerts antitumor effects both as monotherapy and in combination with chemotherapy in transplantable tumor models, i.e., B16-OVA melanoma and EG.7-OVA lymphoma. Subsequently, we proved that sublingual IFN-I in combination with cyclophosphamide (CTX) induces a long-lasting reduction of tumor mass in NeuT transgenic mice that spontaneously develop SDC. Most importantly, tumor shrinkage in NeuT transgenic micewas accompanied by the emergence of tumor-specific cellular immune responses both in the blood and in the tumor tissue. Altogether, these results provide evidence that sublingual IFN holds promise in combination with chemotherapy for the treatment of cancer.

scholarly journals Prognostic Impact of PD-L1 Expression in Malignant Salivary Gland Tumors as Assessed by Established Scoring Criteria: Tumor Proportion Score (TPS), Combined Positivity Score (CPS), and Immune Cell (IC) Infiltrate

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 873 ◽  
Author(s):  
Hanno M. Witte ◽  
Niklas Gebauer ◽  
Daniela Lappöhn ◽  
Vincent G. Umathum ◽  
Armin Riecke ◽  
...  
Keyword(s):  
Salivary Gland ◽  
Poor Prognosis ◽  
Immune Cell ◽  
Salivary Gland Tumors ◽  
Malignant Neoplasms ◽  
Prognostic Impact ◽  
Checkpoint Inhibition ◽  
Duct Carcinoma ◽  
Salivary Gland Carcinomas ◽  
Malignant Salivary Gland Tumors

Background: Malignant neoplasms of the salivary glands are rare, and therapeutic options are limited. Results from recently published studies indicate a possible use for checkpoint inhibition in a subset of patients, but there are no established criteria for programme cell death ligand 1 (PD-L1) scoring in salivary gland carcinomas (SGCs). Methods: In this retrospective study, we present a cohort of 94 SGC patients with full clinical follow-up. We included 41 adenoid cystic carcinomas (AdCC), 21 mucoepidermoid carcinomas (MEC), 16 acinic cell carcinomas (ACC), 12 adenocarcinomas, not otherwise specified (AC, NOS), 2 epithelial-myoepithelial carcinomas (EMC), one salivary duct carcinoma (SDC), and one carcinoma ex pleomorphic adenoma (CA ex PA). Subsequent histopathological analysis was performed with special emphasis on the composition of the immune cell infiltrate (B-/T-lymphocytes). We assessed PD-L1 (SP263) on full slides by established scoring criteria: tumor proportion score (TPS), combined positivity score (CPS) and immune cell (IC) score. Results: We identified significantly elevated CD3+, TP, CP, and IC scores in AC, NOS compared to AdCC, MEC, and ACC. CPS correlated with node-positive disease. Moreover, AC, NOS displayed IC scores of 2 or 3 in the majority (67%) of cases (p = 0.0031), and was associated with poor prognosis regarding progression-free (PFS) (p < 0.0001) and overall survival (OS) (p < 0.0001). CPS correlated with strong nuclear or null p53 staining in AC, NOS but not in other SGCs. Long-lasting partial remission could be achieved in one AC, NOS patient who received Pembrolizumab as third-line therapy. Conclusions: The current study is the first to investigate the use of established scoring criteria for PD-L1 expression in malignant salivary gland tumors. Our findings identify unique characteristics for AC, NOS among the family of SGCs, as it is associated with poor prognosis and might represent a valuable target for immune checkpoint inhibition.

scholarly journals Viruses induce high expression of BAFF by salivary gland epithelial cells through TLR- and type-I IFN-dependent and -independent pathways

2008 ◽  
Vol 38 (4) ◽  
pp. 1058-1064 ◽  
Author(s):  
Marc Ittah ◽  
Corinne Miceli-Richard ◽  
Jacques-Eric Gottenberg ◽  
Jérémie Sellam ◽  
Pierre Eid ◽  
...  
Keyword(s):  
Salivary Gland ◽  
Epithelial Cells ◽  
High Expression ◽  
Type I ◽  
Type I Ifn ◽  
Salivary Gland Epithelial Cells

scholarly journals Elucidating Mechanisms of Antitumor Immunity Mediated by Live Oncolytic Vaccinia and Heat-Inactivated Vaccinia

2021 ◽  
Author(s):  
Weiyi Wang ◽  
Peihong Dai ◽  
Shuaitong Liu ◽  
Ning Yang ◽  
Yi Wang ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Adaptive Immunity ◽  
Antitumor Immunity ◽  
Type I ◽  
Type I Ifn ◽  
Antitumor Effects ◽  
Innate And Adaptive Immunity ◽  
Cytokines And Chemokines ◽  
Immunological Mechanisms

AbstractBackgroundViral-based immunotherapy has the potential to overcome resistance to immune checkpoint blockade (ICB) and to fill the unmet needs of many cancer patients. Oncolytic viruses (OVs) are defined as engineered or naturally occurring viruses that selectively replicate in and kill cancer cells. OVs also induce antitumor immunity. The purpose of this study is to compare the antitumor effects of live OV-GM expressing murine granulocyte-macrophage colony-stimulating factor (mGM-CSF) versus inactivated OV-GM and elucidate the underlying immunological mechanisms.MethodsIn this study, we engineered a replication-competent, oncolytic vaccinia virus (OV-GM) by inserting a murine GM-CSF gene into the thymidine kinase (TK) locus of a mutant vaccinia E3LΔ83N, which lacks the Z-DNA-binding domain of vaccinia virulence factor E3. We compared the antitumor effects of intratumoral (IT) delivery of live OV-GM vs. heat-inactivated OV-GM (heat-iOV-GM) in a murine B16-F10 melanoma bilateral implantation model.ResultsHeat-iOV-GM infection of dendritic cells (DCs) and tumor cells in vitro induces type I IFN and pro inflammatory cytokines and chemokines, whereas live OV-GM does not. IT live OV-GM is less effective in generating systemic antitumor immunity compared with heat-iOV-GM. Similar to heat-iOV-GM, the antitumor effects of live OV-GM also require Batf3-dependent CD103+ dendritic cells. IT heat-iOV-GM induces higher numbers of infiltrating activated CD8+ and CD4+ T cells as well as higher levels of type I IFN, proinflammatory cytokines, and chemokines in the distant non-injected tumors, which is dependent on CD8+ T cells. When combined with systemic delivery of ICB, IT heat-iOV-GM is more effective in eradicating tumors compared with live OV-GM.ConclusionsTumor lysis induced by the replication of oncolytic DNA viruses has a limited effect on the generation of systemic antitumor immunity. The activation of Batf3-dependent CD103+ DCs is critical for antitumor effects induced by both live OV-GM and heat-iOV-GM. Heat-iOV-GM is more potent than live OV-GM in the induction of innate and adaptive immunity in both the injected and distant non-injected tumors. We propose that evaluations of both innate and adaptive immunity induced by IT oncolytic viral immunotherapy at injected and non-injected tumors should be included as potential biomarkers.

scholarly journals Histomorphological study of salivary gland neoplasms: fifteen year study

2020 ◽  
Vol 8 (7) ◽  
pp. 2469
Author(s):  
M. Hemalata ◽  
C. P. Manjula ◽  
Rishitha Nandi
Keyword(s):  
Salivary Gland ◽  
Cell Carcinoma ◽  
Pleomorphic Adenoma ◽  
Mucoepidermoid Carcinoma ◽  
Salivary Gland Tumors ◽  
Salivary Gland Neoplasms ◽  
Benign Tumors ◽  
Duct Carcinoma ◽  
Long Term Outcome ◽  
Female Ratio

Background: The neoplasms of salivary glands are relatively uncommon and represent less than 2% of all human tumors. They are morphologically diverse, with marked heterogeneity among the different subtypes and even within the same tumor. The unpredictability in the long term outcome imposes a significant challenge in the clinical management.Methods: This is a descriptive study done in a tertiary care teaching hospital over a period of 15 years. Patient details were collected from medical case records. All specimens were evaluated for site, laterality, size, nature of the cut surface and intactness of the capsule. Two to 5 representative bits were taken from each specimen and subjected to routine fixation, processing and section cutting followed by Haematoxylin and Eosin staining.Results: A total of 138 salivary gland tumors were diagnosed from patients in the age group of 13 to 90 years with a mean age of 41.8 years. There were 53 (38.4%) males and 85 (61.6%) females with male to female ratio of 1:1.42. There were 115 (83.3%) benign tumors and 23 (16.7%) malignant tumors. Pleomorphic adenoma accounted for 70.3% of all salivary gland tumors followed by mucoepidermoid carcinoma (10.9%), Warthin tumor (8%), basal cell adenoma (2.9%), adenoid cystic carcinoma (2.2%), squamous cell carcinoma (2.2%), myoepithelioma (1.4%), oxyphillic adenoma (0.7%), acinic cell carcinoma (0.7%) and salivary duct carcinoma (0.7%).Conclusions: The salivary gland neoplasms are relatively uncommon head and neck tumors. Parotid gland is the commonest site of occurrence. Pleomorphic adenoma is the commonest benign and mucoepidermoid carcinoma the commonest malignant salivary gland tumor.

scholarly journals Differential interferon-α subtype immune signatures suppress SARS-CoV-2 infection

2021 ◽  
Author(s):  
Jonas Schuhenn ◽  
Toni L Meister ◽  
Daniel Todt ◽  
Thilo Bracht ◽  
Karin Schork ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Therapeutic Potential ◽  
Biological Effects ◽  
Antiviral Drug ◽  
Airway Epithelial Cells ◽  
Interferon Α ◽  
Type I ◽  
Type I Ifn ◽  
Type I Ifns ◽  
Immune Signatures

Type I interferons (IFN-I) exert pleiotropic biological effects during viral infections, balancing virus control versus immune-mediated pathologies and have been successfully employed for the treatment of viral diseases. Humans express twelve IFN-alpha (α) subtypes, which activate downstream signalling cascades and result in distinct patterns of immune responses and differential antiviral responses. Inborn errors in type I IFN immunity and the presence of anti-IFN autoantibodies account for very severe courses of COVID-19, therefore, early administration of type I IFNs may be protective against life-threatening disease. Here we comprehensively analysed the antiviral activity of all IFNα subtypes against SARS-CoV-2 to identify the underlying immune signatures and explore their therapeutic potential. Prophylaxis of primary human airway epithelial cells (hAEC) with different IFNα subtypes during SARS-CoV-2 infection uncovered distinct functional classes with high, intermediate and low antiviral IFNs. In particular IFNα5 showed superior antiviral activity against SARS-CoV-2 infection. Dose-dependency studies further displayed additive effects upon co-administered with the broad antiviral drug remdesivir in cell culture. Transcriptomics of IFN-treated hAEC revealed different transcriptional signatures, uncovering distinct, intersecting and prototypical genes of individual IFNα subtypes. Global proteomic analyses systematically assessed the abundance of specific antiviral key effector molecules which are involved in type I IFN signalling pathways, negative regulation of viral processes and immune effector processes for the potent antiviral IFNα5. Taken together, our data provide a systemic, multi-modular definition of antiviral host responses mediated by defined type I IFNs. This knowledge shall support the development of novel therapeutic approaches against SARS-CoV-2.

Multimodality Treatment and Survival in Sinonasal Minor Salivary Gland Tumors

2019 ◽  
Author(s):  
Sina Torabi ◽  
Todd Spock ◽  
Bruno Cardoso ◽  
Janet Chao ◽  
R. Manes ◽  
...  
Keyword(s):  
Salivary Gland ◽  
Minor Salivary Gland ◽  
Multimodality Treatment ◽  
Salivary Gland Tumors ◽  
Minor Salivary Gland Tumors

PLASMACYTOID DENDRITIC CELLS FUNCTION IN HIV INFECTION

2008 ◽  
Vol 31 (4) ◽  
pp. 13
Author(s):  
Martin Hyrcza ◽  
Mario Ostrowski ◽  
Sandy Der
Keyword(s):  
Dendritic Cells ◽  
Influenza Virus ◽  
Hiv Infection ◽  
Gene Transcription ◽  
Sendai Virus ◽  
Plasmacytoid Dendritic Cells ◽  
Type I Interferons ◽  
Interferon Response ◽  
Type I ◽  
Type I Ifn

Plasmacytoid dendritic cells (pDCs) are innate immune cells able to produce large quantities of type I interferons (IFN) when activated. Human immunodeficiency virus (HIV)-infected patients show generalized immune dysfunction characterized in part by chronic interferon response. In this study we investigated the role of dendritic cells inactivating and maintaining this response. Specifically we compared the IFN geneactivity in pDCs in response to several viruses and TLR agonists. We hypothesized that 1) the pattern of IFN gene transcription would differ in pDCs treated with HIV than with other agents, and 2) that pDCs from patients from different stages of disease would respond differently to the stimulations. To test these hypotheses, we obtained pDCs from 15 HIV-infected and uninfected individuals and treated freshly isolated pDCs with either HIV (BAL strain), influenza virus (A/PR/8/34), Sendai virus (Cantell strain), TLR7 agonist(imiquimod), or TLR9 agonist (CpG-ODN) for 6h. Type I IFN gene transcription was monitored by real time qPCRfor IFNA1, A2, A5, A6, A8,A17, B1, and E1, and cytokine levels were assayed by Cytometric Bead Arrays forTNF?, IL6, IL8, IL10, IL1?, and IL12p70. pDC function as determined by these two assays showed no difference between HIV-infected and uninfected patients or between patients with early or chronic infection. Specifically, HIV did notinduce type I IFN gene expression, whereas influenza virus, Sendai virus and imiquimod did. Similarly, HIV failed to induce any cytokine release from pDCs in contrast to influenza virus, Sendai virus and imiquimod, which stimulatedrelease of TNF?, IL6, or IL8. Together these results suggest that the reaction of pDCs to HIV virus is quantitatively different from the response to agents such as virus, Sendai virus, and imiquimod. In addition, pDCs from HIV-infected persons have responses similar to pDCs from uninfected donors, suggesting, that the DC function may not be affected by HIV infection.

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