scholarly journals The impact of macrophage-cancer cell interaction on the efficacy of photodynamic therapy

2015 ◽  
Vol 14 (8) ◽  
pp. 1403-1409 ◽  
Author(s):  
Mladen Korbelik ◽  
Michael R. Hamblin
Keyword(s):  
Immune Response ◽  
Photodynamic Therapy ◽  
Tumor Cells ◽  
Adaptive Immune Response ◽  
Cell Interaction ◽  
M1 Macrophages ◽  
Adaptive Immune ◽  
Light Delivery ◽  
Dying Cells ◽  
The Impact

PDT has different effects on macrophages in tumors. The photosensitizer (PS) is taken up by M2 TAMS inside the tumor, which are killed upon light delivery. Signaling from these dying cells attracts new M1 macrophages from the circulation that can kill remaining tumor cells and stimulate an adaptive immune response.

scholarly journals Rapid Weight Loss, Central Obesity Improvement and Blood Glucose Reduction Are Associated with a Stronger Adaptive Immune Response Following COVID-19 mRNA Vaccine

Vaccines ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 79
Author(s):  
Mikiko Watanabe ◽  
Angela Balena ◽  
Davide Masi ◽  
Rossella Tozzi ◽  
Renata Risi ◽  
...  
Keyword(s):  
Immune Response ◽  
Weight Loss ◽  
Blood Glucose ◽  
Adaptive Immune Response ◽  
Humoral Response ◽  
Rapid Weight Loss ◽  
Low Carbohydrate Diet ◽  
Adaptive Immune ◽  
Glucose Reduction ◽  
The Impact

Obesity is associated with a poor COVID-19 prognosis, and it seems associated with reduced humoral response to vaccination. Public health campaigns have advocated for weight loss in subjects with obesity, hoping to eliminate this risk. However, no evidence proves that weight loss leads to a better prognosis or a stronger immune response to vaccination. We aimed to investigate the impact of rapid weight loss on the adaptive immune response in subjects with morbid obesity. Twenty-one patients followed a hypocaloric, very-low-carbohydrate diet one week before to one week after the two mRNA vaccine doses. The diet’s safety and efficacy were assessed, and the adaptive humoral (anti-SARS CoV-2 S antibodies, Abs) and cell-mediated responses (IFNγ secretion on stimulation with two different SARS CoV-2 peptide mixes, IFNγ-1 and IFNγ-2) were evaluated. The patients lost ~10% of their body weight with metabolic improvement. A high baseline BMI correlated with a poor immune response (R −0.558, p = 0.013 for IFNγ-1; R −0.581, p = 0.009 for IFNγ-2; R −0.512, p = 0.018 for Abs). Furthermore, there was a correlation between weight loss and higher IFNγ-2 (R 0.471, p = 0.042), and between blood glucose reduction and higher IFNγ-1 (R 0.534, p = 0.019), maintained after weight loss and waist circumference reduction adjustment. Urate reduction correlated with higher Abs (R 0.552, p = 0.033). In conclusion, obesity is associated with a reduced adaptive response to a COVID-19 mRNA vaccine, and weight loss and metabolic improvement may reverse the effect.

scholarly journals Photodynamic Therapy Using a New Folate Receptor-Targeted Photosensitizer on Peritoneal Ovarian Cancer Cells Induces the Release of Extracellular Vesicles with Immunoactivating Properties

2020 ◽  
Vol 9 (4) ◽  
pp. 1185 ◽  
Author(s):  
Martha Baydoun ◽  
Olivier Moralès ◽  
Céline Frochot ◽  
Colombeau Ludovic ◽  
Bertrand Leroux ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Immune Response ◽  
Photodynamic Therapy ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Extracellular Vesicles ◽  
Immune Cells ◽  
Surgical Techniques ◽  
Ovarian Cancer Cells ◽  
The Impact

Often discovered at an advanced stage, ovarian cancer progresses to peritoneal carcinoma, which corresponds to the invasion of the serosa by multiple tumor implants. The current treatment is based on the combination of chemotherapy and tumor cytoreduction surgery. Despite the progress and standardization of surgical techniques combined with effective chemotherapy, post-treatment recurrences affect more than 60% of women in remission. Photodynamic therapy (PDT) has been particularly indicated for the treatment of superficial lesions on large surfaces and appears to be a relevant candidate for the treatment of microscopic intraperitoneal lesions and non-visible lesions. However, the impact of this therapy on immune cells remains unclear. Hence, the objective of this study is to validate the efficacy of a new photosensitizer [pyropheophorbide a-polyethylene glycol-folic acid (PS)] on human ovarian cancer cells and to assess the impact of the secretome of PDT-treated cells on human peripheral blood mononuclear cells (PBMC). We show that PS, upon illumination, can induce cell death of different ovarian tumor cells. Furthermore, PDT using this new PS seems to favor activation of the immune response by inducing the secretion of effective cytokines and inhibiting the pro-inflammatory and immunosuppressive ones, as well as releasing extracellular vesicles (EVs) prone to activating immune cells. Finally, we show that PDT can activate CD4+ and CD8+ T cells, resulting in a potential immunostimulating process. The results of this pilot study therefore indicate that PS-PDT treatment may not only be effective in rapidly and directly destroying target tumor cells but also promote the activation of an effective immune response; notably, by EVs. These data thus open up good prospects for the treatment of micrometastases of intraperitoneal ovarian carcinosis which are currently inoperable.

Salmonella engineered to express CD20-targeting antibodies and a drug-converting enzyme can eradicate human lymphomas

Blood ◽  
2013 ◽  
Vol 122 (5) ◽  
pp. 705-714 ◽  
Author(s):  
Paul E. Massa ◽  
Aida Paniccia ◽  
Ana Monegal ◽  
Ario de Marco ◽  
Maria Rescigno
Keyword(s):  
Immune Response ◽  
Tumor Cells ◽  
Tumor Antigen ◽  
Adaptive Immune Response ◽  
Human Tumors ◽  
Converting Enzyme ◽  
Adaptive Immune ◽  
Key Points

Key PointsSalmonella is engineered to specifically infect tumor cells based on recognition of a tumor antigen by a bacterial-expressed antibody. Once inside, Salmonella can transfer cytotoxic cargos to destroy human tumors even in the absence of an adaptive immune response.

scholarly journals Immune Response to COVID-19

2021 ◽  
Author(s):  
Ricardo Wesley Alberca
Keyword(s):  
Immune Response ◽  
Adaptive Immune Response ◽  
Multiple Organ ◽  
Disease Course ◽  
Angiotensin Converting Enzyme 2 ◽  
Damage And Failure ◽  
Adaptive Immune ◽  
General Aspects ◽  
Inflammatory Molecules ◽  
The Impact

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) invades the host’s cells via the angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2). ACE2 and TMPRSS2 molecules are highly expressed on the respiratory tract but are also expressed in other organs such as kidneys, heart, and intestine, which could partially explain the multiple organ infection, damage, and failure. During the COVID-19 disease course, patients may develop a dysregulation in the immune response, with an exacerbated production of pro-inflammatory molecules and hypercoagulation, which can collaborate to the increase in tissue damage and death. This chapter will cover general aspects of the innate and adaptive immune response during COVID-19, the impact of comorbidities on the immune response to SARS-CoV-2, and the immune response generated by COVID-19 vaccines.

scholarly journals The Paradox of a Phagosomal Lifestyle: How Innate Host Cell-Leishmania amazonensis Interactions Lead to a Progressive Chronic Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Matheus B. Carneiro ◽  
Nathan C. Peters
Keyword(s):  
Immune Response ◽  
Chronic Disease ◽  
Host Cell ◽  
Adaptive Immune Response ◽  
Innate Immune ◽  
Leishmania Amazonensis ◽  
Host Cells ◽  
Adaptive Immune ◽  
Th2 Immunity ◽  
The Impact

Intracellular phagosomal pathogens represent a formidable challenge for innate immune cells, as, paradoxically, these phagocytic cells can act as both host cells that support pathogen replication and, when properly activated, are the critical cells that mediate pathogen elimination. Infection by parasites of the Leishmania genus provides an excellent model organism to investigate this complex host-pathogen interaction. In this review we focus on the dynamics of Leishmania amazonensis infection and the host innate immune response, including the impact of the adaptive immune response on phagocytic host cell recruitment and activation. L. amazonensis infection represents an important public health problem in South America where, distinct from other Leishmania parasites, it has been associated with all three clinical forms of leishmaniasis in humans: cutaneous, muco-cutaneous and visceral. Experimental observations demonstrate that most experimental mouse strains are susceptible to L. amazonensis infection, including the C57BL/6 mouse, which is resistant to other species such as Leishmania major, Leishmania braziliensis and Leishmania infantum. In general, the CD4+ T helper (Th)1/Th2 paradigm does not sufficiently explain the progressive chronic disease established by L. amazonensis, as strong cell-mediated Th1 immunity, or a lack of Th2 immunity, does not provide protection as would be predicted. Recent findings in which the balance between Th1/Th2 immunity was found to influence permissive host cell availability via recruitment of inflammatory monocytes has also added to the complexity of the Th1/Th2 paradigm. In this review we discuss the roles played by innate cells starting from parasite recognition through to priming of the adaptive immune response. We highlight the relative importance of neutrophils, monocytes, dendritic cells and resident macrophages for the establishment and progressive nature of disease following L. amazonensis infection.

scholarly journals How sticky should a virus be? The impact of virus binding and release on transmission fitness using influenza as an example

2014 ◽  
Vol 11 (92) ◽  
pp. 20131083 ◽  
Author(s):  
Andreas Handel ◽  
Victoria Akin ◽  
Sergei S. Pilyugin ◽  
Veronika Zarnitsyna ◽  
Rustom Antia
Keyword(s):  
Immune Response ◽  
Adaptive Immune Response ◽  
Virus Binding ◽  
Adaptive Immune ◽  
Cell Mediated Immune Response ◽  
Infected Cells ◽  
The Right ◽  
The Impact ◽  
Virus Fitness ◽  
Better Than

Budding viruses face a trade-off: virions need to efficiently attach to and enter uninfected cells while newly generated virions need to efficiently detach from infected cells. The right balance between attachment and detachment—the right amount of stickiness—is needed for maximum fitness. Here, we design and analyse a mathematical model to study in detail the impact of attachment and detachment rates on virus fitness. We apply our model to influenza, where stickiness is determined by a balance of the haemagglutinin (HA) and neuraminidase (NA) proteins. We investigate how drugs, the adaptive immune response and vaccines impact influenza stickiness and fitness. Our model suggests that the location in the ‘stickiness landscape’ of the virus determines how well interventions such as drugs or vaccines are expected to work. We discuss why hypothetical NA enhancer drugs might occasionally perform better than the currently available NA inhibitors in reducing virus fitness. We show that an increased antibody or T-cell-mediated immune response leads to maximum fitness at higher stickiness. We further show that antibody-based vaccines targeting mainly HA or NA, which leads to a shift in stickiness, might reduce virus fitness above what can be achieved by the direct immunological action of the vaccine. Overall, our findings provide potentially useful conceptual insights for future vaccine and drug development and can be applied to other budding viruses beyond influenza.

The Impact of IFNλ4 on the Adaptive Immune Response to SARS-CoV-2 Infection

2021 ◽  
Vol 41 (11) ◽  
pp. 407-414
Author(s):  
Michelle Møhlenberg ◽  
Ida Monrad ◽  
Line K. Vibholm ◽  
Stine S.F. Nielsen ◽  
Giacomo Schmidt Frattari ◽  
...  
Keyword(s):  
Immune Response ◽  
Adaptive Immune Response ◽  
Adaptive Immune ◽  
The Impact

scholarly journals Autologous Stem Cell Transplantation Disrupts Adaptive Immune Responses during Rebound Simian/Human Immunodeficiency Virus Viremia

2017 ◽  
Vol 91 (13) ◽  
Author(s):  
Daniel B. Reeves ◽  
Christopher W. Peterson ◽  
Hans-Peter Kiem ◽  
Joshua T. Schiffer
Keyword(s):  
Immune Response ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Primary Infection ◽  
Adaptive Immune Response ◽  
Treatment Interruption ◽  
Viral Loads ◽  
Adaptive Immune ◽  
The Impact

ABSTRACT Primary HIV-1 infection induces a virus-specific adaptive/cytolytic immune response that impacts the plasma viral load set point and the rate of progression to AIDS. Combination antiretroviral therapy (cART) suppresses plasma viremia to undetectable levels that rebound upon cART treatment interruption. Following cART withdrawal, the memory component of the virus-specific adaptive immune response may improve viral control compared to primary infection. Here, using primary infection and treatment interruption data from macaques infected with simian/human immunodeficiency virus (SHIV), we observe a lower peak viral load but an unchanged viral set point during viral rebound. The addition of an autologous stem cell transplant before cART withdrawal alters viral dynamics: we found a higher rebound set point but similar peak viral loads compared to the primary infection. Mathematical modeling of the data that accounts for fundamental immune parameters achieves excellent fit to heterogeneous viral loads. Analysis of model output suggests that the rapid memory immune response following treatment interruption does not ultimately lead to better viral containment. Transplantation decreases the durability of the adaptive immune response following cART withdrawal and viral rebound. Our model's results highlight the impact of the endogenous adaptive immune response during primary SHIV infection. Moreover, because we capture adaptive immune memory and the impact of transplantation, this model will provide insight into further studies of cure strategies inspired by the Berlin patient. IMPORTANCE HIV patients who interrupt combination antiretroviral therapy (cART) eventually experience viral rebound, the return of viral loads to pretreatment levels. However, the “Berlin patient” remained free of HIV rebound over a decade after stopping cART. His cure is attributed to leukemia treatment that included an HIV-resistant stem cell transplant. Inspired by this case, we studied the impact of stem cell transplantation in a macaque simian/HIV (SHIV) system. Using a mechanistic mathematical model, we found that while primary infection generates an adaptive immune memory response, stem cell transplantation disrupts this learned immunity. The results have implications for HIV cure regimens based on stem cell transplantation.

scholarly journals Normal T and B Cell Responses Against SARS-CoV-2 in a Family With a Non-Functional Vitamin D Receptor: A Case Report

2021 ◽  
Vol 12 ◽  
Author(s):  
Martin Kongsbak-Wismann ◽  
Fatima A. H. Al-Jaberi ◽  
Jonas Damgård Schmidt ◽  
Mustafa Ghanizada ◽  
Cecilie Bo Hansen ◽  
...  
Keyword(s):  
Vitamin D ◽  
Immune Response ◽  
General Population ◽  
Vitamin D Receptor ◽  
Adaptive Immune Response ◽  
Cell Responses ◽  
Adaptive Immune ◽  
Vitamin D Signaling ◽  
The Impact

The coronavirus disease 2019 (COVID-19) pandemic has severely impacted daily life all over the world. Any measures to slow down the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and to decrease disease severity are highly requested. Recent studies have reported inverse correlations between plasma levels of vitamin D and susceptibility to SARS-CoV-2 infection and COVID-19 severity. Therefore, it has been proposed to supplement the general population with vitamin D to reduce the impact of COVID-19. However, by studying the course of COVID-19 and the immune response against SARS-CoV-2 in a family with a mutated, non-functional vitamin D receptor, we here demonstrate that vitamin D signaling was dispensable for mounting an efficient adaptive immune response against SARS-CoV-2 in this family. Although these observations might not directly be transferred to the general population, they question a central role of vitamin D in the generation of adaptive immunity against SARS-CoV-2.

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