Academic literature on the topic 'Early immune surveillance'

Cancer immunotherapy has shifted the paradigm in cancer therapy by revitalizing immune responses against tumor cells. Specifically, in primary tumors cancer cells evolve in an immunosuppressive microenvironment, which protects them from immune attack. However, during tumor progression, some cancer cells leave the protective tumor mass, disseminating and seeding secondary organs. These initial disseminated tumor cells (DTCs) should potentially be susceptible to recognition by the immune system in the new host tissues. Although Natural Killer or T cells eliminate some of these DTCs, a fraction escape anti-tumor immunity and survive, thus giving rise to metastatic colonization. How DTCs interact with immune cells and the underpinnings that regulate imperfect immune responses during tumor dissemination remain poorly understood. Uncovering such mechanisms of immune evasion may contribute to the development of immunotherapy specifically targeting DTCs. Here we review current knowledge about systemic and site-specific immune-cancer crosstalk in the early steps of metastasis formation. Moreover, we highlight how conventional cancer therapies can shape the pre-metastatic niche enabling immune escape of newly arrived DTCs.

Chorioangioma is a placental hemangioma is a common, non-trophoblastic benign vascular placental tumour of primitive chorionic mesenchyme. The size of the tumour is important. Smaller tumours are clinically insignificant. Giant chorioangioma more than 4 cm has higher risk of maternal and foetal complications. Early diagnosis is done by imaging techniques. Placental lesions detected on sonography necessitate close surveillance of these pregnancies because of the poor outcome ofpregnancy. We present a 32-year primigravida with placental chorioangioma who went in spontaneous labour and delivered a male baby. The baby was referred to higher centre for further evaluation and revealed mild cardiomegaly. The histopathological examination of placenta helped in the diagnosis of placental chorioangioma.

The role of the immune system in combating tumour progression has been studied extensively. The two branches of the immune response – humoral and cell-mediated – act both independently and in concert to combat tumour progression, the success of which depends on the immunogenicity of the tumour cells. The immune system discriminates between transformed cells and normal cells by virtue of the presence of unique antigens on tumour cells. Despite this, the immune system is not always able to detect and kill cancerous cells because neoplasms have also evolved various strategies to escape immune surveillance. Attempts are being made to trigger the immune system into an early and efficient response against malignant cells, and various therapeutic modalities are being developed to enhance the strength of the immune response against tumours. This review aims to elucidate the tumouricidal role of various components of the immune system, including macrophages, lymphocytes, dendritic cells and complement.

Background Imatinib and dasatinib modulate immune responses in vitro and in vivo. Immunological surveillance in the MRD-situation might be of particular relevance for long-term control or even elimination of CML-repopulating stem cells. Little is known about potential immune-modulatory effects of nilotinib in vivo. The ENEST1st study (NCT01061177) is focused on examining the role of firstline nilotinib therapy in CML-CP - this ENEST1st substudy involves a comprehensive immunological monitoring program.

Melanoma ranks as the fifth most common solid cancer in adults worldwide and is responsible for a significant proportion of skin-tumor-related deaths. The advent of immune checkpoint inhibition with anti-programmed death protein-1 (PD-1) antibodies has revolutionized the adjuvant treatment of high-risk, completely resected stage III/IV melanoma. However, not all patients benefit equally. Current strategies for improving outcomes involve adjuvant treatment in earlier disease stages (IIB/C) as well as perioperative treatment approaches. Interfering with T-cell exhaustion to counteract cancer immune evasion and the immunogenic nature of melanoma is key for anti-PD-1 effectiveness. Yet, the biological rationale for the efficacy of adjuvant treatment in clinically tumor-free patients remains to be fully elucidated. High-dose intermittent sun exposure (sunburn) is a well-known primary risk factor for melanomagenesis. Also, ultraviolet radiation (UVR)-induced immunosuppression may impair anti-cancer immune surveillance. In this review, we summarize the current knowledge about adjuvant anti-PD-1 blockade, including a characterization of the main cell types most likely responsible for its efficacy. In conclusion, we propose that local and systemic immunosuppression, to some extent UVR-mediated, can be restored by adjuvant anti-PD-1 therapy, consequently boosting anti-melanoma immune surveillance and the elimination of residual melanoma cell clones.

Abstract As there is no assay to predict the risk of acute cellular allograft rejection (ACAR), clinicians rely on graft biopsy and aggressive, one-size-fits-all immunosuppression. Endomyocardial biopsy (EMB) is a flawed standard for heart transplant surveillance and diagnosing ACAR, as histological evidence of rejection inherently lags behind molecular biomarkers and suffers from variability. Noninvasive alternatives to EMB in ACAR surveillance, including gene profiling and donor-derived cell-free DNA, also measure lagging indicators of ACAR. A minimally invasive surveillance method is urgently needed to quantify early risk of rejection for minimizing biopsy and personalizing immunosuppression. We have developed porous biomaterial “scaffolds” for minimally-invasive sampling. These scaffolds amass immune cells producing biomarkers as an immunological niche. We identified predictive biomarkers of ACAR conserved in both in murine heterotopic heart transplant and skin transplant through the remote scaffold. We identified 43 highly differentially-expressed genes as organ-agnostic biomarkers of T cell-mediated rejection. These novel biomarkers differentiate between pre-symptomatic ACAR and recipients with healthy allografts, without invasive biopsy. Scaffold cell capture technology provides a leading indicator of ACAR by monitoring tissue-specific immune responses associated with allograft rejection. This implantable scaffold enables minimally invasive histological evaluation and molecular calculation of the early risk of rejection to reduce the frequency of routine EMB and personalize immune suppression that could prolong transplant life while minimizing risk. Supported by the Falk Medical Research Trust Catalyst Award and Transformational Award

Cancer vaccines are a type of immune therapy that seeks to modulate the host’s immune system to induce durable and protective immune responses against cancer-related antigens. The little clinical success of therapeutic cancer vaccines is generally attributed to the immunosuppressive tumor microenvironment at late-stage diseases. The administration of cancer-preventive vaccination at early stages, such as pre-malignant lesions or even in healthy individuals at high cancer risk could increase clinical efficacy by potentiating immune surveillance and pre-existing specific immune responses, thus eliminating de novo appearing lesions or maintaining equilibrium. Indeed, research focus has begun to shift to these approaches and some of them are yielding encouraging outcomes.

By increasing the activity of the immune system, immune checkpoint inhibitors (ICPI) can have adverse inflammatory effects, which are referred to as immune-related adverse effects (irAEs). In this review, we present the recommendations for the appropriate identification and treatment of irAEs associated with ICPI to increase the safety and effectiveness of therapy with these immuno-oncological drugs. Several guidelines to manage irAEs adopted by different American and European societies in the field of oncology were identified. A narrative review of the several strategies adopted to manage irAEs was performed. With close clinical surveillance, ICPI can be used even in patients who have mild irAEs. Moderate to severe events require early detection and appropriate treatment, particularly in patients with a history of transplantation or pre-existing autoimmune disease. In most cases, adverse reactions can be treated with the interruption of treatment and/or supportive therapy, which includes, in serious adverse reactions, the administration of immunosuppressants. The identification and treatment of irAEs in the early stages may allow patients to resume therapy with ICPI. This review is an instrument to support healthcare professionals involved in the treatment and monitoring of patients who are administered ICPI, contributing to the timely identification and management of irAEs.

Early detection is the key in managing side effects because immune-related adverse events (irAEs) are becoming more serious, and their onset time differs. In our hospital, we conducted an outpatient pharmacist clinic for early detection of irAEs by self-care practice for the cases of immune checkpoint inhibitor administration. As a result of a retrospective survey of 207 cases, the percentage of irAEs found by pharmacist’s suggestion of the outpatient pharmacist clinic increased over time, and a high detection ratio was obtained even for irAEs with a late onset time. The incidence of serious irAEs was higher than that in the immediate post-marketing surveillance, and different factors were considered. Although there were some problems, the outpatient pharmacist clinic had a certain effect.

Le neutrophile est la cellule immunitaire la plus représentée dans le sang chez l’Homme, dont la migration au site inflammatoire est rapide. Le rôle du neutrophile a largement été décrit dans des contextes infectieux, auto-immunitaires et allergiques mais reste controversé dans le cancer, notamment dans les mécanismes d’immunosurveillance précoce. Le neutrophile se révèle être une population hétérogène tant phénotypiquement que fonctionnellement. L’origine et la compréhension de l’hétérogénéité des neutrophiles est un sujet émergent et croissant, mais aucune étude à ce jour ne décrit l’évolution de l’hétérogénéité des neutrophiles à différents stades. L’objectif de ma thèse est de caractériser cette hétérogénéité au sein des tissus au cours de la tumorigenèse, à partir de deux modèles d’études. Mon premier projet s’est intéressé au cancer colorectal (CCR) chez l’Homme de par l’accès privilégié à des échantillons de tissus adjacents colorectaux (AT), de tissus prénéoplasiques (polypes, P) et d'adénocarcinomes (ADK), frais, synchrones et pairés à partir de patients subissant des colectomies partielles ou totales. Des quantifications protéomiques démontrent que les neutrophiles représentent la principale augmentation de cellules immunitaires innées au sein de l'ADK. Pour la première fois, les profils transcriptomiques de neutrophiles triés et de leurs partenaires cellulaires par RNA-seq et single cell RNA-seq (scRNA-seq) au cours de la tumorigenèse ont été établis et intégrées pour déchiffrer l'hétérogénéité, l’évolution et les interactions cellulaires clés des neutrophiles, au cours du CCR. Alors que le microenvironnement du P et de l’ADK sont similaires et distinct de l’AT, le transcriptome des neutrophiles de P et d’AT sont corrélés mais différents de ceux de l’ADK. Ces résultats suggèrent une niche pré-inflammatoire dans le P favorable aux modifications des neutrophiles, précédant l'inflammation cancéreuse, favorisant la migration et l’activation des cellules myéloïdes. Les neutrophiles du P présentent des propriétés fonctionnelles (e.g. dégranulation, activation, production de cytokines) tandis que les neutrophiles de l'ADK présentent un état “d’épuisement” associé à un profil plutôt pro-tumoral (i.e. perte de fonctions canoniques et profil pro-tumoral). Le scRNA-seq de neutrophiles triés identifie 8 clusters distincts, dont deux sont spécifiquement enrichis dans l’AT et l’ADK. Le cluster enrichi dans l’AT est associé à des signatures anti-tumorales tandis que le cluster associé à l'ADK démontre des caractéristiques pro-tumorales, basées sur des analyses d’enrichissement de signatures issues de données publiques. Les analyses de trajectoire démontrent un continuum de l’AT, à P et ADK avec 3 trajectoires distinctes, où un cluster unique de neutrophiles exprimant des gènes induits par les interférons et enrichi dans l’ADK se distingue des autres. Le second projet s’est basé sur un modèle murin de carcinogenèse mammaire spontanée MMTV-NeuT pour lequel, à la différence du modèle chez l’Homme, nous avons accès aux différents stades tumoraux mais également au sang et aux organes lymphoïdes primaire (moelle osseuse) et secondaire (rate). Les analyses transcriptomiques de neutrophiles triés révèlent des états phénotypiques et fonctionnels distincts selon l’organe et le stade tumoral analysé. De manière originale, nous avons mis en évidence l’existence de neutrophiles EpCAM+ uniques aux tissus tumoraux et constituant 60 à 90% des neutrophiles totaux au cours de la tumorigenèse. L’expression d’EpCAM n’est pas endogène mais semblerait provenir de fragments membranaires exogènes à la surface du neutrophile, suggérant un mécanisme de trogocytose voire de trogoptose des cellules prénéoplasiques et tumorales. De futures études fonctionnelles permettront d’élucider le mécanisme et le rôle des neutrophiles EpCAM+
The neutrophil is the most abundant immune cell in the human blood that migrates rapidly to the inflammatory site. The role of neutrophils has been extensively described in infectious, autoimmune, and allergic contexts, but it remains controversial in cancer, particularly in early immune surveillance mechanisms. Neutrophils are a heterogeneous population, both phenotypically and functionally. The origin and understanding of neutrophil heterogeneity are emerging and increasingly studied, albeit to date, no study has described the evolution of neutrophil heterogeneity at different stages. The aim of my thesis is to characterize this heterogeneity within tissues during tumorigenesis, using two models. My first project focused on colorectal cancer (CRC) in humans, taking advantage of a privileged access to fresh, synchronous, and paired adjacent colorectal tissue samples (AT), preneoplastic tissues (polyps, P), and adenocarcinomas (ADK), from patients undergoing partial or total colectomies. Proteomic quantification demonstrated that neutrophils represent the main increase in the innate immune compartment within ADK. For the first time, transcriptomic profiles of FACS-sorted neutrophils and their cellular partners using RNA-seq and single-cell RNA-seq (scRNA-seq) throughout tumorigenesis were established and integrated to decipher the heterogeneity, evolution, and key cellular interactions of neutrophils in CRC. While the microenvironment of P and ADK were similar and distinct from AT, the transcriptome of P and AT neutrophils were correlated but different from ADK-associated neutrophils. These results suggest a pre-inflammatory niche in P that favors neutrophil modifications, preceding cancer-related inflammation, promoting migration and activation of myeloid cells. P-associated neutrophils exhibited functional properties (e.g. degranulation, activation, cytokine production), while ADK-associated neutrophils showed an "exhausted" state associated with a more pro-tumoral profile (i.e. loss of canonical functions and pro-tumoral profile). scRNA-seq of FACS-sorted neutrophils identified 8 distinct clusters, two of which were specifically enriched in AT and ADK. The AT-enriched cluster was associated with anti-tumoral signatures, while the ADK-enriched cluster demonstrated pro-tumoral characteristics, based on enrichment analyses of publicly available data signatures. Trajectory analyses showed a continuum from AT to P and ADK with three distinct trajectories, where a unique ADK-enriched cluster of neutrophils expressing interferon-stimulated genes stood out from the others. The second project was based on a mouse model of spontaneous mammary carcinogenesis, MMTV-NeuT, for which, unlike the human model, we have access to breast tissues at different stages as well as blood and primary (bone marrow) and secondary (spleen) lymphoid organs. Transcriptomic analysis of FACS-sorted neutrophils revealed distinct phenotypic and functional states depending on the organ and tumor stage. Interestingly, we unveiled the existence of a unique EpCAM+ neutrophil population in tumor tissues, representing 60 to 90% of total neutrophils throughout tumorigenesis. EpCAM expression was not endogenous but seemed to originate from exogenous membrane fragments on the surface of neutrophils, suggesting a mechanism of trogocytosis or even trogoptosis of preneoplastic and tumor cells. Further functional studies will elucidate the mechanism and the role of EpCAM+ neutrophils

This chapter describes the increasing global problem of new and emerging infections, many zoonotic, ranging from the recently described Middle East respiratory syndrome (MERS) to bacteria now resistant to all locally available antimicrobial agents. The environmental, human, technological, and microbial factors contributing to disease emergence are assessed. Changes in environment and land use result in the spread of vector-borne diseases into new areas, and global travel and trade may introduce pathogens to non-immune populations. The breakdown of health services following political change or during conflict can result in the resurgence of previously controlled communicable diseases. The importance of collaboration between human and veterinary health services is emphasized, and the UK ‘DATER’ strategy (Detection, Assessment, Treatment, Escalation, Recovery) for dealing with pandemic influenza is applied to new and emerging infections. Finally, the role of internet-based, syndromic surveillance to create early awareness of new infections is considered.

Surveillance against tumors is governed by both intrinsic (non-immune) and extrinsic (immune) surveillance. While research on non-immune surveillance started as early as the 1960s when it was demonstrated that cell environment within and around can induce tumor-suppressing mechanisms, a major part of the progress is missing compared to immune surveillance. Part of the reason could be due to the fact that immune surveillance is seen to have more potential in therapeutic application in curing cancerous tumors compared to non-immune surveillance mechanisms. Many of the non-immune mechanisms are still under investigation as theories, although a few studies have shown their possibility. Contrary to this, there is a plethora of studies on immune surveillance. The immune system has been proven to have a role in the surveillance against tumors, thus conferring a certain degree of protection. However, not all tumor cells are successfully detected by innate immunity, and many of them have developed strategic ways of escaping adaptive immunity. The immunosurveillance in both animal models and humans shows overwhelmingly that cells with immunodeficiencies are more susceptible to tumor development. However, it is confounding that even immune-competent individuals develop tumors, and thus a significant process is responsible. Thus, immunoediting was proposed as a theory to explain why tumors can escape immunosurveillance. This chapter provides detailed evidence from animal and human tumors and analyses the mechanisms, pathways, and components implicated in tumor immune surveillance. The findings suggest that while immune surveillance could be the key to promoting immune function against the development of tumors, there is more research and understanding needed in the various mechanisms and cells implicated. This is because most, if not all, of the therapeutic studies using immune effectors have proved to be poor in preventing, treating, or regulating the development of tumors.

For a fungal pathogen to successfully infect, colonize and spread inside a susceptible host, it must have overcome the host immune responses. The early recognition of the fungal pathogen-associated molecular patterns (PAMPS) by the host’s pattern recognition receptors (PRRs) results in the establishment of anti-fungal immunity. Although, our immune system has evolved several processes to combat these pathogens both at the innate and adaptive immune levels. These organisms have developed various escape strategies to evade the recognition by the host\'s innate immune components and thus interfering with host immune mechanisms. In this chapter, we will summarize the major PRRs involved in sensing fungal PAMPS and most importantly the fungal tactics to escape the host\'s innate immune surveillance and protective mechanisms.

Bordetella pertussis is an exclusively human pathogen found worldwide in all populations. Complications of pertussis including bronchopneumonia, failure to thrive from post-tussive vomiting, cerebral hypoxia leading to brain damage, and death are strongly concentrated in infants. The similarity in mortality profile with age between countries that are markedly different with respect to demography, health systems, socioeconomic status, and surveillance systems is striking. It is because infants are most likely to suffer serious complications of infection or die that prevention of pertussis in infants is the primary goal of immunization programmes. Of all the vaccine-preventable infections, pertussis remains the most epidemiologically challenging to understand. This is partly because of surveillance issues but also the lack of an established correlate of protection that allows susceptible and immune individuals to be distinguished. These factors are compounded by our imperfect understanding of the mechanism of protection from acellular and whole-cell vaccines, and the product-specific differences in efficacy and effectiveness. It can therefore be difficult for policymakers to be confident about the optimal number and timing of primary doses and how many and at what age booster doses should be given in their setting, as reflected in the plethora of schedules in use throughout the world. There are even greater challenges for the World Health Organization when attempting to make global policy as lessons learned in one setting may not appear to apply in others. What is clear is that high coverage early in infancy with three doses of an effective vaccine greatly reduces pertussis mortality and severe morbidity in all settings and that many infants in resource-poor settings are still deprived of that benefit.

Abstract The mammalian immune system has developed methods for the surveillance of both extracellular and intracellular compartments for 'non-self'. This surveillance is effected by antigen-specific receptors on T lymphocytes, whose natural ligands are short peptides complexed with major histocompatibility complex (MHC) encoded class I or class II molecules. MHC molecules are integral membrane proteins, specifically designed-to bind a diverse set of peptides and to deliver them to the cell surface for recognition by T cells. The structural features of MHC molecules and their peptide binding specificities are discussed in Chapter 4 and in recent reviews (1-4). Here I will focus on the molecular mechanisms used to generate MHC-binding peptides and to deliver them to the appropriate MHC molecules. Early experiments based on the ability to differentially induce or inhibit antigen presentation by MHC class I versus MHC class II molecules suggested that differ ent mechanisms were utilized for the loading of these two classes of molecules with peptides (reviewed in refs 5-7). More recently, it has become possible to isolate and characterize the peptides found naturally associated with MHC molecules; the data derived from such studies are generally consistent with the notion of separate pathways for the derivation of class I- and class II-associated peptides. In general, MHC class I-associated peptides are derived from proteins that are either synthesized on the host cell's own ribosomes (3, 4), or which are artificially introduced into the cytoplasm of living cells (8, 9). In contrast, peptides found naturally associated with MHC class II molecules are derived predominantly from the extracellular portions of cell surface proteins, or from proteins endocytosed from the extracellular medium (10-14).

Progressive neurodegenerative diseases represent some of the largest growing treatment challenges for public health in modern society. These diseases mainly progress due to aging and are driven by microglial surveillance and activation in response to changes occurring in the aging brain. The lack of efficacious treatment options for Alzheimer’s disease (AD), as the focus of this review, and other neurodegenerative disorders has encouraged new approaches to address neuroinflammation for potential treatments. Here we will focus on the increasing evidence that dysbiosis of the gut microbiome is characterized by inflammation that may carry over to the central nervous system and into the brain. Neuroinflammation is the common thread associated with neurodegenerative diseases, but it is yet unknown at what point and how innate immune function turns pathogenic for an individual. This review will address extensive efforts to identify constituents of the gut microbiome and their neuroactive metabolites as a peripheral path to treatment. This approach is still in its infancy in substantive clinical trials and requires thorough human studies to elucidate the metabolic microbiome profile to design appropriate treatment strategies for early stages of neurodegenerative disease. We view that in order to address neurodegenerative mechanisms of the gut, microbiome and metabolite profiles must be determined to pre-screen AD subjects prior to the design of specific, chronic titrations of gut microbiota with low-dose antibiotics. This represents an exciting treatment strategy designed to balance inflammatory microglial involvement in disease progression with an individual’s manifestation of AD as influenced by a coercive inflammatory gut.