Chimeric antigen receptor T cells (CAR-T cells) are proving their value in hematological cancers as B-cell acute lymphoid leukemia (B-ALL). This success is in great part due to the chosen target antigen, the lineage marker CD19, which is expressed by leukemia blasts and B lymphocytes, which are not crucial. For solid tumors, the challenge is greater because antigen expression is highly heterogeneous

Immunotherapy has emerged as a potent and effective treatment for multiple cancer types and the engineering of T cells through the expression of chimeric antigen receptor (CAR) against tumors has shown remarkable potentials. This review outlined clinical applications of CAR-T cell therapy in hematological malignancies and solid tumors, with a focus on the main challenges related to the safety and efficacy

The field of cell therapy is leading a paradigm shift in drug development. The recent convergence of several fields including immunology, genetics and synthetic biology now allows the introduction of artificial receptors and design of entire genetic circuitries to finely program the behavior of injected cells. The poster child of these next-generation living drugs are T cells expressing chimeric antigen

Chimeric antigen receptor T (CAR-T) cell therapy is a recent therapeutic acquisition in the field of oncology, the first one approved being represented by tisagenlecleucel, followed short after by the approval of axicabtagene ciloleucel. Because this product is derived from T-cells, there are several lessons that can be learned from T-cell biology to better understand CAR-T cells. Thus, in this review

Genetically engineered T-cell therapies have the adeptness to modernize and revolutionize the treatment of cancer. Cancer immunotherapy, by depending on this fundamental recognition method, supports the antitumor viability of T-cells and extends adaptive immunity by encouraging adoptive transfer of genetically engineered T-cells. T-cells assume a key part in cell-mediated immunity as well as to make

The SARS-CoV-2 virus infection quickly crossed the geographical barriers of the place where it emerged in Asia. From an epidemic caused by a respiratory virus in humans, fast, it became a pandemic. This shows us clearly that, despite the knowledge accumulated over the last century, we are still highly vulnerable to the attack of microorganisms, mainly viruses. This is aggravated when the virus in question

Chimeric antigen receptor (CAR) T cell therapy has demonstrated remarkable responses in patients with certain haematological malignancies. However, its efficacy in solid tumors still remains disappointing. There are many factors that can potentially limit the effect of CAR T cell therapy in solid tumors. The infiltration, survival and persistence of CAR-T cells have faced numerous challenges for solid

The pandemic caused by the SARS-CoV-2 has made new treatments a goal for the scientific community. One of these treatments is Ivermectin. Here we discussed the hypothesis of dysbiosis caused by the use of Ivermectin and the possible impacts in neuroinflammatory diseases after the end of the pandemic.

The COVID-19 pandemic has imposed urgency to answer numerous questions about the control of viral infections and the dual immune response of protection of and damage to the host, with the purpose of finding specific and efficient treatments and strategies for prevention of infection. The association between severe cases of the disease and overactivation of the immune response has raised the hypotheses

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of the COVID-19 pandemic, has become a global health emergency. The damage and threat posed by this virus to nearly every country in the world have far exceeded those of the other six previous coronaviruses, including Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome (SARS-CoV) combined

Our investigations of antigens for pathogenic T cells in autoimmune diabetes led to the discovery of hybrid insulin peptides as T cell epitopes. T cells reactive to hybrid insulin peptides can be found at high frequency in the nonobese diabetic mouse model of type 1 diabetes and are also present in human patients. Hybrid insulin peptides can also be administered to mice in a tolerogenic form, thereby

I am writing this chapter to reflect of my memories spanning at the time that I have first met the late Eli Sercarz and succeeded to earn my PhD degree under his titulage and traineeship. My first experience was at the time when Eli was recruited at UCLA as a new Assistant Professor in Immunology and I was in my undergraduate senior year. His teaching course in Fundamental Immunology was revolutionary

In this memoir-style essay, I have narrated the evolution of my scientific career, as deeply influenced by my PhD training and the mentorship of Professor Eli Sercarz. Starting in his lab, and continuing to my own laboratory, many of the questions we have pursued link in some way to Eli's ideas. In this essay, I have summarized the path that I followed after graduating from his lab and highlight findings

Currently the epidemic of SARS-CoV-2-caused COVID-19 is a major threat to global public health. The latest clinical data, laboratory results, and autopsy information are summarized herein to provide a brief review of the significant issues surrounding SARS-CoV-2 and COVID-19. In this review, we also cover research on the ways in which the virus enters the human body, general clinical symptoms, immunopathological

This article is about my amazing immunological journey for more than a decade with Eli Sercarz as an achaarya, which in Sanskrit means enlightened mentor. My training and routine interactions with colleagues not only at Eli's laboratory but at University of California at Los Angeles, La Jolla Institute for Immunology, Torrey Pines Institute for Molecular Studies, and University of California, San Diego

In December 2019, outbreak of a novel coronavirus flared in Wuhan, the capital city of Hubei province, China. The identified pathogen was an enveloped RNA betacoronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The outbreak was declared a pandemic by the World Health Organization (WHO), because the continual spread of this deadly and highly infectious virus is a health

Operational tolerance (OT) is the phenomenon occurring in human renal and liver transplantation in which the body does not reject the organ after discontinuing immunosuppression for at least a year. We revisited the data generated by The Brazilian Multicenter Study on Operational Tolerance involving different conceptual fields − antigen-specific cytokine response, immune cell numbers and repertoire

This article is a tribute to Eli Sercarz and draws on his proposal of a hierarchical order of T-cell determinants in antigen presentation and T-cell activation. Here I revisit the concept of dominance and crypticity in the context of lymphocyte cooperation in the generation of the adaptive immune response, with emphasis on Th-Th cooperation. The remarks made in this article serve as a basis for a reassessment

The physicochemical properties of an antigen (Ag) influence the type, specificity, as well as duration of emerging immune responses. Like immune responses arising to nominal protein Ags, reactivities to protozoan parasites, Plasmodium falciparum and P. berghei, the causative agents of human and mouse malaria, respectively, are shaped by the form of the parasite. While repeated natural exposures to

Acute rheumatic fever (ARF) is caused by an autoimmune response to throat infection with Streptococcus pyogenes in individuals who present some susceptibility genes. Rheumatic heart disease (RHD) is the major sequela and can cause heart failure and premature mortality. The disease is mediated by humoral and cellular immune responses. In this review, we present the major events that can trigger heart

Coronavirus disease 2019 (COVID-19) consists of a severe involvement of the lower respiratory tract leading to an acute respiratory syndrome. But there exist other infectious respiratory syndromes that have the same initial respiratory symptoms, show similar pattern in the size of the antigenic proteins and release comparable cytokines pathways, but with an unlike response magnitude. Here we propose

Coronavirus disease (COVID-19), caused by the virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had a huge impact on global human health and was declared a worldwide distributed pandemic by the World Health Organization. SARS-CoV-2 has strong transmission and pathogenicity; so far, there are more than 16,000,000 cases of infections around the world and COVID-19 has caused more

A silent revolution has occurred in our understanding of how T cell-mediated immunity protects the host from recrudescent pathogens and how it fits into occurrences of autoimmunity and allergies. Under the new paradigm, the hitherto unknown noncirculatory, tissue-resident memory T cells (TRM ) constitute the host defense sentinels posted in diverse anatomic compartments and they are the key actors

Immunity in infants and young children must tolerate a myriad of new antigens that the newborn encounters after birth. We dedicated many years to defying the innate and adaptive mononuclear cell repertoire in pediatric subjects to conclude that immune regulation differs in children and adults and dominates immune functions in babies.

Ample evidence exists for activation of invariant natural killer T (iNKT) cells in a sterile manner by endogenous ligands or microbial antigens from the commensal flora, indicating that iNKT cells are not truly self-tolerant. Their controlled autoreactivity state is disturbed in many types of sterile inflammatory disease, resulting in their central role in modulating autoimmune responses. This review

In humans and mice, susceptibility to infections and autoimmunity increases with age due to age-associated changes in innate and adaptive immune responses. Aged innate cells are also less active, leading to decreased naive T- and B-cell responses. Aging innate cells contribute to an overall heightened inflammatory environment. Naive T and B cells undergo cell-intrinsic age-related changes that result

This brief review is written in memory of Eli Sercarz, a colleague who among many achievements, pioneered and revitalized early-life immunity, a field that is of high relevance to child health. For a long time, the neonatal stage was viewed as a window during which exposure to antigen (Ag) induces immune tolerance. In early 1990, however, it was discovered that the newborn mouse given Ag on the day

Like all of us, cells proceed through stages of life. In this whimsical review, aspects of several such stages, including birth, growth, aging, death, and "afterlife," are considered, with a special emphasis on cells of the immune system. Discussed along the way are asymmetric division of activated, naive cluster of differentiation 8+ T cells, c-Myc and polyamines in lymphocyte function and aging,

Posttranslational modifications (PTMs) such as protein arginine methylation are involved in the regulation of diverse cellular processes such as epigenetic modifications, DNA damage response (DDR), RNA processing, signal transduction, and immune responses. Protein methyltransferases (PRMTs), which mediate arginine methylation, have been studied because of their dysregulation in several diseases. PRMT5

Autoimmunity results from the breakdown of immune tolerance to defined target self antigens. Like any foreign antigen, a self antigen is continuously processed by antigen-presenting cells (APCs) and its epitopes are displayed by the major histocompatibility complex on the cell surface (dominant epitopes). However, this self antigen fails to induce a T cell response as the T cells against its dominant

Macrophages are cells of the myeloid lineage with important roles not only in immune regulation and tissue repair, but also in pathological states such as autoimmune disease and cancer. A plethora of macrophage subtypes exist with distinct phenotypes and functions, not least within the tumor microenvironment (TME) of solid tumors. The abundant macrophages located within the TME are often referred to

The autoimmune disease multiple sclerosis (MS) is driven by T cells that are reactive to self-antigens of the brain and spinal cord. Many drugs have been developed to treat MS, but we believe that immune-specific targeting of pathogenic T cells may be a better approach for treatment. This type of therapy identifies specific components of the self-reactive T-cell repertoire that would undergo similar

Eli Sercarz pioneered epitope recognition by T cells. Studying mice, he made the seminal observation decades ago that epitope dominance is so unpredictable with mixed MHC haplotypes that he coined it aleatory, for dice-like. Accordingly, for every individual there is a unique potential epitope space that is defined by the polymorphic and polygenic MHC molecules (restriction elements) expressed. Of

The contribution of Eli E. Sercarz to immunology and immunopathology has been remarkable and achieved many milestones in the understanding of the processes of the mechanisms fine-tuning immune responses. A part of his work was dedicated to the study of the deep complexity of the lymphocyte T cell repertoire and its importance during the physiologic development and disease, such as clonal heterogeneity

We identified a druggable defect in IL-2 receptor (IL-2R) signaling by comparing the response of regulatory T cells (Tregs) of autoimmune disease patients to that of healthy controls. This defect was in the inhibition of Treg desensitization and was shared across various autoimmune diseases. Low-dose IL-2 stimulation results in maintained pSTAT5 expression for > 4 h, allowing the Treg transcriptome

COVID-19 infection tends to be more lethal in older persons than in the young; death results from an overactive inflammatory response, leading to cytokine storm and organ failure. Here we describe immune regulation of the inflammatory response phenotype as emerging from a process that is analogous to machine-learning algorithms used in computers. We briefly describe some strategic similarities between

We have previously demonstrated that natural killer (NK) cells are the main immune effectors that can mediate selection and differentiation of different cancer stem cells and undifferentiated tumors via lysis and secreted or membrane-bound interferon-γ and tumor necrosis factor-α, respectively. This leads to growth inhibition and tumor metastasis curtailment. In this review, we present an overview

T lymphocytes undergo carefully orchestrated programming during development in the thymus and subsequently during differentiation in the periphery. This intricate specification allows for cell-type and context-specific transcriptional programs that regulate immune responses to infection and malignancy. Epigenetic changes, including histone modifications and covalent modification of DNA itself through

The immune system is a potent defense mechanism regulating tumor development and progression. However, immune cells are often functionally compromised in cancer patients, and tumor rejection does not follow successful induction of a CTL response. This is, in part, due to the existing conflict between the tumor system and an unfavorable tumor microenvironment (TME) that is able to neutralize or paralyze

Coronavirus disease 2019 (COVID-19) poses a great public health challenge worldwide. While studies on the effects of SARS-CoV-2 on immune cell function continue to progress, we know very little about the significance of depletion of key immune effectors by the virus in the mortality and morbidity of the disease. This commentary reviews what is known thus far about the effects of the virus on natural

Mucosa-associated invariant T cells (MAIT cells) are unconventional, innate-like T lymphocytes with remarkable effector and immunoregulatory functions. They are abundant in the human peripheral blood and also enriched in mucosal layers and in the lungs, SARS-CoV-2's main ports of entry. Once activated, MAIT cells produce inflammatory cytokines and cytolytic effector molecules quickly and copiously

Pancreatic cancer is one of the most lethal kinds of cancer; numerous patients die from it every year all over the word. Fewer than 5% of people with pancreatic cancer survive death and recover. Recent evidence suggests that inflammation parameters, such as Th17 cells and Tregs, affect the progression and even the diagnosis and treatment of pancreatic cancer. In the inflammation process, T lymphocytes

Therapeutic antibodies and nanotherapeutic drugs are of great concern due to their widespread use against numerous diseases worldwide. They are frequently used for targeted therapy under the assumption that they cause fewer side effects than nontargeted drugs. Despite their specificity and particular design for therapeutic actions, they might still exhibit unintended adverse effects in the immune system

Human immunodeficiency virus (HIV) infection is associated with greatly increased risk for development of non-Hodgkin lymphoma (NHL). Nearly all acquired immunodeficiency syndrome (AIDS)-associated NHL (AIDS-NHL) is of B-cell origin. Two major mechanisms are believed to contribute to the genesis of AIDS-NHL: (1) loss of immunoregulation of Epstein-Barr virus (EBV)+ B cells, resulting from impaired

Most chronic diseases, caused by lifestyle factors, appear to be linked to inflammation. Inflammation is activated mechanistically, and nuclear factor-κB (NF-κB) is a significant mediator. NF-κB, one of the most studied transcription factors, was first identified in the nucleus of B lymphocytes almost three decades ago. This protein has a key function in regulating the human immune system, and its

Cardiovascular disease (CVD) is the number one cause of death in the United States and worldwide. The most common cause of cardiovascular disease is atherosclerosis, or formation of fatty plaques in the arteries. Low-density lipoprotein (LDL), termed "bad cholesterol", is a large molecule comprised of many proteins as well as lipids including cholesterol, phospholipids, and triglycerides. Circulating

Dendritic cells (DCs) and macrophages (MΦs) are antigen-presenting phagocytic cells found in many peripheral tissues of the human body, including the blood, lymph nodes, skin, and lung. They are vital to maintaining steady-state respiration in the human lung based on their ability to clear airways while also directing tolerogenic or inflammatory responses based on specific stimuli. Over the past three

The innate immune system serves as the first line of defense to protect the host from pathogen infection. As a first step, the pattern recognition receptors (PRRs) recognize pathogen-associated molecular patterns (PAMPs), such as non-self DNA derived from pathogens, and damage-associated molecular patterns (DAMPs), such as self DNA released from damaged or injured cells. Sensing of such DNAs elicits

Among the inflammatory myopathies, anti-tRNA-synthetase syndrome (ASyS) is a severe autoimmune condition characterized by extramuscular involvement, affecting especially the lungs. ASyS specific serological markers are anti-tRNA-synthetase autoantibodies, among which anti-histidyl-tRNA-synthetase is the most common. In the past decades, ASyS has been distinguished by unique histological features attributed

Chronic inflammation is one of the most evident and common pathological conditions leading to deregulated osteoclastogenesis and bone remodeling. Tumor necrosis factor (TNF) as a pleiotropic cytokine plays a key role, not only in inflammation, but also in bone erosion in diseases associated with bone loss. TNF can stimulate the proliferation of osteoclast precursors and, in most conditions, act together

Inflammatory bowel disease (IBD) is caused by the interplay of various factors. It occurs in genetically susceptible people due to dysregulated immune responses to several unknown antigens, including those derived from the commensal microbiota. Effector T-helper cells, especially TH17 cells, are considered a major driver of disease progression. The endogenous resident counterparts of effector T-helper

Lamtor1 is a lysosome-anchored protein that was first reported in 2009. In this review, we describe the discovery and intracellular functions of Lamtor1, as well as physiological roles of Lamtor1 in immune cells, namely, macrophages, CD4+ helper T-cells, and regulatory T-cells. To date, the following three strains of immune cell-specific conditional Lamtor1-knockout mice have been generated: myeloid-specific

Fibroblasts are a major structural cell in the human lung, being responsible for the production of extracellular matrix components that provide the intricate structure necessary for correct lung function. Generally located in the submucosa, fibroblasts do not usually directly interact with the commensal microbes that we now know are resident in the airways. However, during situations in which alveolar

By acquiring, processing, and presenting both foreign and self-antigens, dendritic cells (DCs) initiate T cell activation that is shaped through the immunomodulatory functions of a variety of cell-membrane-bound molecules including BTLA-HVEM, CD40-CD40L, CTLA-4-CD80/CD86, CD70-CD27, ICOS-ICOS-L, OX40-OX40L, and PD-L1-PD-1, as well as several key cytokines and enzymes such as interleukin-6 (IL-6), IL-12

Eosinophils (Eos) are prominent inflammatory cells found in the sputum, airways, and airway walls during and after exacerbations of allergic asthma. These cells are potent secretors of a wide array of cytotoxic granule proteins, cytokines, and lipid mediators involved in the initiation and maintenance of the Th2-type inflammatory reaction. Even though respiratory viral and bacterial infections are

Exosomes, nanovesicles shown to regulate physiological processes in vivo, have been implicated in pathological conditions including cancer, autoimmune disease, infectious disease, neurodegenerative disease, and allograft rejection. Studies of lung transplant recipients with primary graft dysfunction, respiratory viral infection, and (acute) rejection have demonstrated circulating exosomes containing

The past decade has seen enormous progress in cancer immunotherapy. Checkpoint inhibitors are a class of immunotherapy that act to recruit endogenous T cells of a patient's immune system against cancer-associated peptide- MHC antigens. In this process, mutated antigenic peptides referred to as neoantigens often serve as the target on cancer cells that are recognized by the T cell receptor (TCR) on

Communication between the nervous and immune systems is required for the body to regulate physiological homeostasis. Beta-adrenergic receptors expressed on immune cells mediate the modulation of immune response by neural activity. Activation of beta-adrenergic signaling results in suppression of antitumor immune response and limits the efficacy of cancer immunotherapy. Beta-adrenergic signaling is

Mouse cathelin-related antimicrobial peptide (CRAMP) and its homologue human cathelicidin (LL-37) play active roles in innate immune responses, angiogenesis, and wound healing. In addition, LL-37/CRAMP fends off microbes and protects against infections in the colon, where the epithelium is exposed to myriad of enteric pathogens. It is increasingly recognized that LL-37/CRAMP maintains colon mucosal

Signaling from the T cell receptor for antigen turns on the physiological response of a T cell. The canonical TCR signaling pathway relies on early activation of the Src kinase LCK. This step initiates a cascade of events that lead not only to the phenotypic changes that characterize effector T cells but also to the activation of negative regulatory mechanisms that stop early TCR signaling. These mechanisms