Abstract:
:Construction of an optimal vaccine against tumors relies on the availability of appropriate tumor-specific antigens capable to stimulate CD4+ T helper cells (TH) and CD8+ cytolytic T cells (CTL). CTL are considered the major effectors of the anti-tumor adaptive immune response as they recognize antigens presented on MHC class I (MHC-I) molecules usually expressed in all cells and thus also in tumors. However, attempts to translate in clinics vaccination protocols based only on tumor-specific MHC-I-bound peptides have resulted in very limited, if any, success. We believe failure was mostly due to inadequate triggering of the TH arm of adaptive immunity, as TH cells are necessary to trigger and maintain the proliferation of all the immune effector cells required to eliminate tumor cells. In this review, we focus on a novel strategy of anti-tumor vaccination established in our laboratory and based on the persistent expression of MHC class II (MHC-II) molecules in tumor cells. MHC-II are the restricting elements of TH recognition. They are usually not expressed in solid tumors. By genetically modifying tumor cells of distinct histological origin with the MHC-II transactivator CIITA, the physiological controller of MHC-II gene expression discovered in our laboratory, stable expression of all MHC class II genes was obtained. This resulted in tumor rejection or strong retardation of tumor growth in vivo in mice, mediated primarily by tumor-specific TH cells as assessed by both depletion and adoptive cell transfer experiments. Importantly these findings led us to apply this methodology to human settings for the purification of MHC-II-bound tumor specific peptides directly from tumor cells, specifically from hepatocarcinomas, and the construction of a multi-peptide (MHC-II and MHC-I specific) immunotherapeutic vaccine. Additionally, our approach unveiled a noticeable exception to the dogma that dendritic cells are the sole professional antigen presenting cells (APC) capable to prime naïve TH cells, because CIITA-dependent MHC-II expressing tumor cells could also perform this function. Thus, our approach has served not only to select the most appropriate tumor specific peptides to activate the key lymphocytes triggering the anti-tumor effector functions but also to increase our knowledge of intimate mechanisms governing basic immunological processes.
journal_name
Front Immunoljournal_title
Frontiers in immunologyauthors
Accolla RS,Ramia E,Tedeschi A,Forlani Gdoi
10.3389/fimmu.2019.01806subject
Has Abstractpub_date
2019-07-30 00:00:00pages
1806issn
1664-3224journal_volume
10pub_type
杂志文章,评审abstract::Acute pancreatitis (AP) is a common and devastating inflammatory disorder of the pancreas. However, there are still no effective treatments available for the disease. Therefore, it is important to discover new therapeutic targets and strategies for better treatment and prognosis of AP patients. Toll-like receptor 3 (T...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2019.00980
更新日期:2019-05-03 00:00:00
abstract::Treatment with the macrolide antibiotic azithromycin (AZM) is an important intervention for controlling infection of children with Bordetella pertussis and as a prophylaxis for preventing transmission to family members. However, antibiotics are known to have immunomodulatory effects independent of their antimicrobial ...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2018.01764
更新日期:2018-07-30 00:00:00
abstract::The incidence of allergic diseases continues to rise. Cross-sectional and longitudinal studies have indicated that allergic diseases occur in a time-based order: from atopic dermatitis and food allergy in infancy to gradual development into allergic asthma and allergic rhinitis in childhood. This phenomenon is defined...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2020.01907
更新日期:2020-08-27 00:00:00
abstract::Tumor necrosis factor (TNF) is widely accepted as a tumor-suppressive cytokine via its ubiquitous receptor TNF receptor 1 (TNFR1). The other receptor, TNFR2, is not only expressed on some tumor cells but also on suppressive immune cells, including regulatory T cells and myeloid-derived suppressor cells. In contrast to...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2018.01170
更新日期:2018-05-28 00:00:00
abstract::Gestational age-dependent immune intolerance at the maternal-fetal interface might be a contributing factor to placental pathology and adverse pregnancy outcomes. Although the intrauterine setting is highly choreographed and considered to be a protective environment for the fetus, unscheduled inflammation might overwh...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2019.00718
更新日期:2019-04-05 00:00:00
abstract::Leprosy, a disease caused by the intracellular parasite Mycobacterium leprae or Mycobacterium lepromatosis, has affected humans for more than 4,000 years and is a stigmatized disease even now. Since clinical manifestations of leprosy patients present as an immune-related spectrum, leprosy is regarded as an ideal model...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2020.00567
更新日期:2020-04-16 00:00:00
abstract::Piperlongumine (PL), a natural small molecule derived from the Piper longum Linn plant, has received growing interest as a prooxidative drug with promising anticancer properties. Yet, the influence of PL on primary human T cells remained elusive. Knowledge of this is of crucial importance, however, since T cells in pa...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.01172
更新日期:2020-06-12 00:00:00
abstract:Background:The aging process leads to a potential decline in immune function and adversely affects the gut microbiota. To date, many in vitro and in vivo studies focused on the application of synbiotics (prebiotics combined with probiotics) as a promising dietary approach to affect gut microbiota composition and improv...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2017.01443
更新日期:2017-12-12 00:00:00
abstract::Systemic Sclerosis (SSc) is a complex auto-immune connective tissue disease combining inflammatory, vasculopathic and fibrotic manifestations. Skin effectively recapitulates the main pathogenic processes and therefore is a good organ to decipher the disease pathophysiology, which remains unclear. However, culturing pr...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.566607
更新日期:2020-10-07 00:00:00
abstract::While rodent cancer models are essential for early proof-of-concept and mechanistic studies for immune therapies, these models have limitations with regards to predicting the ultimate effectiveness of new immunotherapies in humans. As a unique spontaneous, large animal model of cancer, the value of conducting studies ...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2019.02935
更新日期:2020-01-17 00:00:00
abstract::The genome has the ability to respond in a precise and co-ordinated manner to cellular signals. It achieves this through the concerted actions of transcription factors and the chromatin platform, which are targets of the signaling pathways. Our understanding of the molecular mechanisms through which transcription fact...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2015.00499
更新日期:2015-09-29 00:00:00
abstract::How B cells contribute to protective immunity against parasitic nematodes remains unclear, with their importance as accessory cells underexplored. In this study, anti-CD20 monoclonal antibody (α-CD20 mAb)-mediated depletion of B cells from C57BL/6 mice revealed an important role for B cells in supporting Th2 immune re...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2019.02842
更新日期:2019-12-10 00:00:00
abstract::Emerging and re-emerging viruses pose a significant public health challenge around the world, among which RNA viruses are the cause of many major outbreaks of infectious diseases. As one of the early lines of defense in the human immune system, RIG-I-like receptors (RLRs) play an important role as sentinels to thwart ...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2018.01379
更新日期:2018-06-20 00:00:00
abstract::Eosinophils are an enigmatic white blood cell, whose immune functions are still under intense investigation. Classically, the eosinophil was considered to fulfill a protective role against parasitic infections, primarily large multicellular helminths. Although eosinophils are predominantly associated with parasite inf...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2018.02763
更新日期:2018-11-26 00:00:00
abstract::Human pathogen Campylobacter jejuni is a significant risk factor for the development of long-term intestinal dysfunction although the cellular and molecular mechanisms remain scantily defined. IL-23 is an emerging therapeutic target for the treatment of inflammatory intestinal diseases, however its role in C. jejuni-d...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.579615
更新日期:2021-01-06 00:00:00
abstract::Age-related deficits in the immune system have been associated with an increased incidence of infections, autoimmune diseases, and cancer. Human B cell populations change quantitatively and qualitatively in the elderly. However, the function of human B-1 cells, which play critical anti-microbial and housekeeping roles...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2019.00483
更新日期:2019-03-19 00:00:00
abstract::Chemokines and their cognate receptors have been identified as major factors initiating and governing cell movement and interaction. These ligands and their receptors are expressed on a wide variety of cells and act during steady-state migration as well as inflammatory recruitment. CCR6 is a non-promiscuous chemokine ...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2013.00194
更新日期:2013-07-15 00:00:00
abstract::Clinical management of neuropathic pain is unsatisfactory, mainly due to its resistance to the effects of available analgesics, including opioids. Converging evidence indicates the functional interactions between chemokine and opioid receptors and their influence on nociceptive processes. Recent studies highlight that...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.615327
更新日期:2020-12-21 00:00:00
abstract::A balance between co-inhibitory and co-stimulatory signals in the tumor microenvironment (TME) is critical to suppress tumor development and progression, primarily via maintaining effective immunosurveillance. Aberrant expression of immune checkpoints (ICs), including programmed cell death protein 1 (PD-1), cytotoxic ...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2020.01469
更新日期:2020-07-14 00:00:00
abstract::Therapy with Tyrosine Kinase Inhibitors (TKI) aiming stable deep molecular response is the gold standard to treat Chronic Myeloid Leukemia (CML). NKT-like cells (CD3+CD56+) combine characteristics of T and NK cells. The physiopathological role of these cells remains unknown although the literature refers their associa...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2019.02493
更新日期:2019-10-22 00:00:00
abstract::The development of stable and long-circulating liposomes provides protection of the drug cargo from degradation and increases tumor drug delivery, leading to the design of liposome formulations with great potential in cancer therapy. However, despite the sound pharmacologic basis, many liposomal as well as other nanop...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2017.00416
更新日期:2017-04-06 00:00:00
abstract::Clematichinenoside AR (C-AR) is a triterpene saponin isolated from the root of Clematis manshurica Rupr., which is a herbal medicine used in traditional Chinese medicine for the treatment of arthritis. C-AR exerts anti-inflammatory and immunosuppressive properties, but little is known about its action in the suppressi...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2016.00532
更新日期:2016-12-07 00:00:00
abstract::The limited efficacy of seasonal influenza vaccines is usually attributed to ongoing variation in the major antigenic targets for protective antibody responses including hemagglutinin (HA) and neuraminidase (NA). Hence, vaccine development has largely focused on broadening antigenic epitopes to generate cross-reactive...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.01207
更新日期:2020-06-19 00:00:00
abstract::Antibody deficiency or hypogammaglobulinemia can have primary or secondary etiologies. Primary antibody deficiency (PAD) is the result of intrinsic genetic defects, whereas secondary antibody deficiency may arise as a consequence of underlying conditions or medication use. On a global level, malnutrition, HIV, and mal...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2019.00033
更新日期:2019-02-08 00:00:00
abstract::Infectious diseases are still a significant cause of morbidity and mortality worldwide. Despite the progress in drug development, the occurrence of microbial resistance is still a significant concern. Alternative therapeutic strategies are required for non-responding or relapsing patients. Chimeric antigen receptor (C...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2019.02711
更新日期:2019-11-21 00:00:00
abstract::As we have suggested, epigenetic factors, such as microRNAs (miRNAs), can interact with genetic programs to regulate B cell functions, thereby informing antibody and autoantibody responses. We have shown that histone deacetylase (HDAC) inhibitors (HDI) inhibit the differentiation events critical to the maturation of t...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2015.00627
更新日期:2015-12-14 00:00:00
abstract::Psoriatic arthritis (PsA) is an inflammatory arthritis, characterized by inflammation of entheses and synovium, leading to joint erosions and new bone formation. It affects 10-30% of patients with psoriasis, and has an estimated prevalence of approximately 1%. PsA is considered to be primarily an autoimmune disease, d...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2018.01533
更新日期:2018-07-16 00:00:00
abstract:PURPOSE OF REVIEW:The standard treatment options for systemic lupus erythematosus (SLE) are focused on non-specific immunosuppression. Over the past few years, scientific studies and ongoing clinical trials have shifted the paradigm with rapid advances in developing biologics and small molecules. A number of monoclonal...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2018.02658
更新日期:2018-11-16 00:00:00
abstract::Virus infected immune cells can rapidly respond to the invader by activating the inflammasome and as a consequence release proinflammatory cytokines and eventually die by pyroptosis. In human adenovirus-5 (Ad5) infected THP-1 cells, inhibition of NLRP3 inflammasome activation was demonstrated by a decreased secretion ...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2019.02791
更新日期:2019-11-28 00:00:00
abstract::Many pathogens, including the malaria parasite Plasmodium falciparum, display high levels of polymorphism within T-cell epitope regions of proteins associated with protective immunity. The T-cell epitope variants are often non-cross-reactive. Herein, we show in a murine model, which modifies a protective CD8 T-cell ep...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2017.00115
更新日期:2017-02-14 00:00:00