scholarly journals Immunotherapy to treat malignancy in patients with pre-existing autoimmunity

2020 ◽  
Vol 8 (1) ◽  
pp. e000356 ◽  
Author(s):  
Patrick Boland ◽  
Anna C Pavlick ◽  
Jeffrey Weber ◽  
Sabina Sandigursky
Keyword(s):  
Autoimmune Disease ◽  
Autoimmune Diseases ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Retrospective Data ◽  
Prospective Data ◽  
The Past ◽  
Increased Risk ◽  
Autoimmune Conditions ◽  
The Relationship

In the past 10 years, immune checkpoint inhibitors (ICIs) have become an additional pillar of cancer therapy by activating the immune system to treat a number of different malignancies. Many patients receiving ICIs develop immune-related adverse events (irAEs) that mimic some features of classical autoimmune diseases. Unfortunately, patients with underlying autoimmune conditions, many of whom have an increased risk for malignancy, have been excluded from clinical trials of ICIs due to a concern that they will have an increased risk of irAEs. Retrospective data from patients with autoimmune diseases and concomitant malignancy treated with ICIs are encouraging and suggest that ICIs may be tolerated safely in patients with specific autoimmune diseases, but there are no prospective data to guide management. In this manuscript, we review the relationship between pre-existing autoimmune disease and irAEs from checkpoint inhibitors. In addition, we assess the likelihood of autoimmune disease exacerbations in patients with pre-existing autoimmunity receiving ICI.

Depression and the risk of autoimmune disease: a nationally representative, prospective longitudinal study

2015 ◽  
Vol 45 (16) ◽  
pp. 3559-3569 ◽  
Author(s):  
N. W. Andersson ◽  
L. N. Gustafsson ◽  
N. Okkels ◽  
F. Taha ◽  
S. W. Cole ◽  
...  
Keyword(s):  
Autoimmune Disease ◽  
Autoimmune Diseases ◽  
Dose Response ◽  
Disease Incidence ◽  
Population Based ◽  
Prospective Longitudinal Study ◽  
Increased Risk ◽  
Autoimmune Conditions ◽  
Nationally Representative ◽  
Prospective Longitudinal

Background.Autoimmune diseases are associated with substantial morbidity and mortality, yet the etiology remains unclear. Depression has been implicated as a risk factor for various immune-related disorders but little is known about the risk of autoimmune disease. This study examined the association between depression and the risk of autoimmune disease, and investigated the temporal and dose-response nature of these relationships.Method.A prospective population-based study including approximately 1.1 million people was conducted using linked Danish registries. Depression and autoimmune diseases were diagnosed by physicians and documented in medical records. In total, 145 217 individuals with depression were identified between 1995 and 2012. Survival analyses were used to estimate the relative risk of autoimmune disease among those with, compared to without, depression. Analyses were adjusted for gender, age, and co-morbid mental disorders.Results.Depression was associated with a significantly increased risk of autoimmune disease [incidence rate ratio (IRR) 1.25, 95% CI 1.19–1.31], compared to those without a history of depression. Results suggest a general increased risk of autoimmune diseases following the onset of depression during first year (IRR 1.29, 95% CI 1.05–1.58), which remained elevated for the ensuing 11 years and beyond (IRR 1.53, 95% CI 1.34–1.76). Findings did not support a dose-response relationship.Conclusions.Depression appears to be associated with an increased risk of a range of autoimmune diseases. Depression may play a role in the etiology of certain autoimmune conditions. If replicated, findings could highlight additional clinical implications in the treatment and management of depression. Future studies are needed to investigate the possible social, genetic, and neurobiological underpinnings of these relationships.

Toxicities of single agent and combination immune checkpoint inhibitors in patients with autoimmune diseases.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14176-e14176
Author(s):  
Samuel Cytryn ◽  
Elizaveta Efuni ◽  
Sabina Sandigursky
Keyword(s):  
Overall Survival ◽  
Combination Therapy ◽  
Autoimmune Diseases ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Single Agent ◽  
Combination Group ◽  
Safety And Efficacy ◽  
Increased Risk

e14176 Background: Autoimmunity is associated with increased risk of malignancy. However, patients with pre-existing autoimmune diseases (AIDs) have been excluded from trials of immune checkpoint inhibitors (ICIs) known to cause immune activation and lead to immune related adverse events (irAEs). Data is limited on the safety and efficacy of these agents when used in AID patients and physicians are therefore wary to use them in this at-risk population. Methods: We conducted a single institution retrospective study to evaluate the safety and efficacy of ICI therapy in patients with pre-existing AIDs from 2011 to 2018. Primary endpoints were irAEs and AID flares. The secondary endpoint was overall survival (OS). Results: Of 84 total patients, 70 (83%) received ICI monotherapy and 14 (17%) received combination therapy. AIDs included: rheumatic 40 (48%), dermatologic 25 (30%), endocrine 16 (19%) and gastrointestinal 14 (17%) diseases of which 18 (21%) were on immune suppression. Combination therapy was associated with higher rates of severe grade 3-4 irAEs in 5/14 (36%) patients versus 8/70 (11%) with monotherapy (p = 0.022). ICIs were discontinued due to irAEs in 10/84 (12%) of all patients; 4/14 (29%) in the combination group and 6/70 (9%) in the monotherapy group (p = 0.057). While 32 patients (38%) had at least one AID flare, ICI was only permanently discontinued in 2 patients. Flare rates were higher for combination use: 8/14 (57%) compared to 23/70 (33%) for monotherapy (p = 0.086). Combination therapy was associated with higher median OS 27.8 months [95% CI 11.4-44.3] compared to monotherapy 12.3 months [95% CI 9.7-14.8] (p = 0.0007). OS had a positive correlation with flare (p = 0.007) and severe irAEs (p = 0.037). Conclusions: Our data suggest that rates of irAEs in patients with pre-existing AIDs are similar to those reported in the literature with single agent ICIs. While risk of severe irAEs and flares is increased with combination therapy, they are associated with overall survival. In our cohort, irAEs and flares were manageable and in most patients did not require permanent discontinuation for monotherapy or combination therapy suggesting that ICIs should be offered to this population, albeit with caution.

Laryngeal Manifestations of Autoimmune Diseases

2020 ◽  
Vol 5 (2) ◽  
pp. 439-456
Author(s):  
Jenny L. Pierce
Keyword(s):  
Autoimmune Disease ◽  
Autoimmune Diseases ◽  
Patient Outcomes ◽  
Correct Diagnosis ◽  
Upper Airway ◽  
Clinical Implications ◽  
Laryngeal Function ◽  
The Past ◽  
Referral Practices ◽  
Timely Referral

Purpose This review article provides an overview of autoimmune diseases and their effects on voice and laryngeal function. Method A literature review was conducted in PubMed. Combinations of the following keywords were used: “autoimmune disease and upper airway,” “larynx,” “cough,” “voice,” “dysphonia,” and “dyspnea.” Precedence was given to articles published in the past 10 years due to recent advances in this area and to review articles. Ultimately, 115 articles were included for review. Results Approximately 81 autoimmune diseases exist, with 18 of those highlighted in the literature as having laryngeal involvement. The general and laryngeal manifestations of these 18 are discussed in detail, in addition to the clinical implications for a laryngeal expert. Conclusions Voice, breathing, and cough symptoms may be an indication of underlying autoimmune disease. However, these symptoms are often similar to those in the general population. Appropriate differential diagnosis and timely referral practices maximize patient outcomes. Guidelines are provided to facilitate correct diagnosis when an autoimmune disease is suspected.

scholarly journals From Oncogenic Signaling Pathways to Single-Cell Sequencing of Immune Cells: Changing the Landscape of Cancer Immunotherapy

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2278
Author(s):  
Afshin Derakhshani ◽  
Zeinab Rostami ◽  
Hossein Safarpour ◽  
Mahdi Abdoli Shadbad ◽  
Niloufar Sadat Nourbakhsh ◽  
...  
Keyword(s):  
Single Cell ◽  
Signaling Pathways ◽  
Immune Cells ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Cancer Development ◽  
Immune Checkpoints ◽  
Single Cell Sequencing ◽  
Increased Risk

Over the past decade, there have been remarkable advances in understanding the signaling pathways involved in cancer development. It is well-established that cancer is caused by the dysregulation of cellular pathways involved in proliferation, cell cycle, apoptosis, cell metabolism, migration, cell polarity, and differentiation. Besides, growing evidence indicates that extracellular matrix signaling, cell surface proteoglycans, and angiogenesis can contribute to cancer development. Given the genetic instability and vast intra-tumoral heterogeneity revealed by the single-cell sequencing of tumoral cells, the current approaches cannot eliminate the mutating cancer cells. Besides, the polyclonal expansion of tumor-infiltrated lymphocytes in response to tumoral neoantigens cannot elicit anti-tumoral immune responses due to the immunosuppressive tumor microenvironment. Nevertheless, the data from the single-cell sequencing of immune cells can provide valuable insights regarding the expression of inhibitory immune checkpoints/related signaling factors in immune cells, which can be used to select immune checkpoint inhibitors and adjust their dosage. Indeed, the integration of the data obtained from the single-cell sequencing of immune cells with immune checkpoint inhibitors can increase the response rate of immune checkpoint inhibitors, decrease the immune-related adverse events, and facilitate tumoral cell elimination. This study aims to review key pathways involved in tumor development and shed light on single-cell sequencing. It also intends to address the shortcomings of immune checkpoint inhibitors, i.e., their varied response rates among cancer patients and increased risk of autoimmunity development, via applying the data from the single-cell sequencing of immune cells.

scholarly journals Association between Inflammatory Conditions and Alzheimer’s Disease Age of Onset in Down Syndrome

2021 ◽  
Vol 10 (14) ◽  
pp. 3116
Author(s):  
Florence Lai ◽  
Nathaniel Mercaldo ◽  
Cassandra M. Wang ◽  
Giovi G. Hersch ◽  
Herminia Diana Rosas
Keyword(s):  
Down Syndrome ◽  
Age Of Onset ◽  
Vitamin B12 Deficiency ◽  
Inflammatory Conditions ◽  
Increased Risk ◽  
Wide Range ◽  
High Prevalence ◽  
Autoimmune Conditions ◽  
B12 Deficiency ◽  
The Relationship

Adults with Down syndrome (DS) have an exceptionally high prevalence of Alzheimer disease (AD), with an earlier age of onset compared with the neurotypical population. In addition to beta amyloid, immunological processes involved in neuroinflammation and in peripheral inflammatory/autoimmune conditions are thought to play important roles in the pathophysiology of AD. Individuals with DS also have a high prevalence of autoimmune/inflammatory conditions which may contribute to an increased risk of early AD onset, but this has not been studied. Given the wide range in the age of AD onset in those with DS, we sought to evaluate the relationship between the presence of inflammatory conditions and the age of AD onset. We performed a retrospective study on 339 adults with DS, 125 who were cognitively stable (CS) and 214 with a diagnosis of AD. Data were available for six autoimmune conditions (alopecia, celiac disease, hypothyroidism, psoriasis, diabetes and vitamin B12 deficiency) and for one inflammatory condition, gout. Gout was associated with a significant delay in the age of AD onset by more than 2.5 years. Our data suggests that inflammatory conditions may play a role in the age of AD onset in DS. Further studies are warranted.

scholarly journals Abdominal surgery in autoimmune and autoimmune-related diseases: A review

2021 ◽  
Vol 6 (2) ◽  
pp. 76-87
Author(s):  
Erdal Uysal ◽  
◽  
Mehmet Dokur ◽  
Gokturk Maralcan
Keyword(s):  
Autoimmune Disease ◽  
Early Detection ◽  
Abdominal Surgery ◽  
Autoimmune Diseases ◽  
High Mortality ◽  
Indirect Effects ◽  
Mortality And Morbidity ◽  
Abdominal Organs ◽  
The Relationship ◽  
Significant Mortality

Autoimmune diseases can have a widespread effect throughout the system and can cause high mortality and morbidity, depending on their involvement in the abdominal organs and systems. Most of the abdominal organs are damaged as a result of the direct or/ and indirect effects of autoimmune diseases. Therefore, abdominal surgeries should be performed to eliminate any complications related to these effects. There could be a significant relationship between abdominal surgery and autoimmune and autoimmune-related diseases. The aim of this study was to reveal the possible relationship between autoimmune and autoimmune-related diseases that cause significant mortality and morbidity. In this way, we further aimed at increasing the awareness of clinicians on this subject, along with providing them with the related publications on autoimmune and autoimmune-related diseases and abdominal surgery. Taking all these into consideration, autoimmune and autoimmune-related diseases can also influence the abdominal organs. The influence may be directly related to the involvement of the organ and system as a result of the autoimmune disease or indirectly related to the influence of the organs and systems. Such influence leading to complications may require urgent or elective abdominal surgery, which can further cause high mortality and morbidity. Therefore, it is significant for all clinicians, especially surgeons, to be aware of the relationship between autoimmune diseases and abdominal surgery. The early detection and treatment of the complications related to the abdominal involvement of autoimmune and autoimmune-related diseases could decrease mortality and morbidity.

Dynamic relationships among tumor, immune response, and microbiota

2019 ◽  
Vol 3 (1) ◽  
pp. 41
Author(s):  
Takuya Tsunoda ◽  
Kazunori Shimada ◽  
Naoki Uchida ◽  
Shinichi Kobayashi ◽  
Yasutsuna Sasaki
Keyword(s):  
Molecular Mechanisms ◽  
Checkpoint Inhibitors ◽  
Advanced Cancer Patients ◽  
Cancer Treatments ◽  
Disease Etiology ◽  
The Past ◽  
Dynamic Relationships ◽  
The Relationship ◽  
Generation Sequencing

Recently, the analysis of microbiota has been of interest not only for the clarification of the molecular mechanisms of disease etiology, but also the discovery of novel strategies for treatment. Following the development of "next-generation" sequencing, novel areas have been discovered in microbiota; however, in oncology, the relationships between microbiota and cancer have not been fully clarified. In recent literature, surprisingly, detection of gut microbiota in tumor issue itself has been reported. Microbiota might play an important role in carcinogenesis. However, this phenomenon is not well understood, and research in this area has just begun. In the past five years, a paradigm shift has occurred in cancer treatment due to immunotherapy. Immunotherapy has made cure possible even in advanced cancer patients with not only melanoma but also non-small cell lung cancer and others. In this review, we discuss the mechanisms of novel immunotherapies, checkpoint inhibitors, and the relationship between microbiota and immunotherapy. It is of significance to clarify this relationship because it may lead to the discovery of predictive markers for immunotherapy and promote clinical efficacy. Finally, we also mention our activities in the construction of a big database for information on immunotherapy and microbiota, which may lead to excellent possibilities of discovering novel strategies for more effective cancer treatments, and may accelerate the alteration of cancers to the classification of chronic nonfatal disease.

Abstract 15395: Immune Checkpoint Inhibitors for Cancer Are Associated With Increased Venous Thromboembolism Events

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Jingyi Gong ◽  
Zsofia Drobni ◽  
Raza Alvi ◽  
Sean Murphy ◽  
Sarah Hartmann ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Immune Activation ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Massachusetts General Hospital ◽  
Control Period ◽  
Fold Increase ◽  
Vein Thrombosis ◽  
Increased Risk

Introduction: Immune checkpoint inhibitors (ICI) lead to immune activation, increased inflammation and cancer cell death. Both immune activation and inflammation are critical pathobiological drivers for venous thromboembolism (VTE). There are no robust data testing the effect of ICIs on the risk of developing VTE. Methods: This is a retrospective study of 2854 patients who received ICIs at Massachusetts General Hospital, Boston, MA. VTE events, defined as a composite of deep vein thrombosis (DVT) or pulmonary embolism (PE), were identified by individual chart review and were blindly adjudicated using standard criteria. A case-crossover design was applied with an “at-risk period” defined as the two-year period after and the “control period” as the two years prior to treatment. Incidence rate ratio (IRR) was calculated using Poisson’s regression. Results: Immune checkpoint inhibitor use increased VTE risk by 1.84-fold from 4.85 per 100-person years to 8.91 per 100 person-years (IRR 1.84, 95% confidence interval: 1.54 - 2.19, p <0.001). Of the individual components, there was a 2.44-fold increase in DVT risk (2.30 to 5.58 per 100 person-years) and 1.68-fold increase in PE risk (2.96 to 5.00 per 100 person-years). Comparing patients with and without a VTE event, those with a VTE event after ICI initiation had a higher rate of prior VTE, lung cancer, urothelial cancer, and a higher platelet count and white blood cell count at baseline. At 6 months post ICI initiation, 165 (8.6%) patients had a VTE event and of these patients 136 (7.1%) had no prior VTE. Conclusions: Patients with cancer treated with ICIs are at increased risk of developing VTE. Whether prophylaxis for VTE among patients starting an ICI reduces this risk is unclear.

Abstract 14600: Pre-existing Autoimmune Disease and the Risk for Cardiovascular and Non-cardiovascular Immune Mediated Adverse Events With Immune Checkpoint Inhibitors

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Charlotte Lee ◽  
Zsofia D Drobni ◽  
Amna Zafar ◽  
Raza M Alvi ◽  
Sean P Murphy ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Autoimmune Disease ◽  
Adverse Events ◽  
Immune Checkpoint ◽  
Cardiovascular Events ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Skin Toxicity ◽  
Significant Difference

Introduction: The use of immune checkpoint inhibitors (ICIs) is associated with an increase in cardiovascular events. The mechanism is likely related to immune activation and inflammation. Patients with pre-existing autoimmune disease have a baseline increased risk for cardiovascular disease and have been traditionally excluded from clinical trials of ICIs. There is limited data on the cardiovascular and non-cardiovascular safety of ICIs in these patients. Methods: This was a retrospective study of 2845 patients treated with an ICI at the Massachusetts General Hospital. This cohort was screened by individual chart review for patients with a diagnosis of an autoimmune disease prior to ICI therapy. These autoimmune patients were compared to controls at a 1:2 ratio. Baseline characteristics and risk of cardiovascular and non-cardiovascular immune related adverse events (iRAEs) were compared. Cardiovascular events were a composite of myocardial infarction (MI), percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG), stroke, transient ischemic attack (TIA), deep venous thrombosis (DVT), pulmonary embolism (PE), or myocarditis. Results: 93 patients had a diagnosis of an autoimmune disease prior to ICI. These patients were more likely to be older and to have a history of coronary artery disease, heart failure, chronic kidney disease, hypertension and diabetes mellitus. There were 12 events over a median follow-up period of 300 days. There was no significant difference in composite of cardiovascular events in follow-up (13 vs. 9.1%, autoimmune vs. none, P =0.41). The individual cardiovascular event rates were as follows: MI (4.3 vs. 0.5%, P =0.04), PCI (0 vs. 0.5%, P =1), CABG (0. vs. 0.5%, P =1), stroke (0 vs. 0%), TIA (0 vs. 0.5%, P =1), DVT (5.4 vs. 2.2%, P =0.17), PE (1.1 vs. 4.8%, P =0.17), and myocarditis (2.2 vs. 1.1%, P =0.60). There was an increased rate of pneumonitis (14 vs. 4%, P <0.001) and skin toxicity (16 vs. 0%, P <0.001). Conclusions: Patients with pre-existing autoimmune disease treated with an ICI had a higher baseline cardiovascular risk but did not have a significant increase in cardiovascular events in an unadjusted analysis. These patients did, however, have an increased rate of pneumonitis and skin toxicity after ICI.

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