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Tumor immunotherapy, represented by immune checkpoint blocking and chimeric antigen receptor (CAR) T cell therapy, has achieved promising results in clinical applications. However, it faces challenges that hinder its further development, such as limited response rates and poor tumor permeability. The efficiency of tumor immunotherapy is also closely linked to the structure and function of the immune microenvironment where the tumor resides. Recently, nanoparticle‐based tumor immune microenvironment (TIME) modulation strategies have attracted a great deal of attention in cancer immunotherapy. This is primarily due to the distinctive physical characteristics of nanoparticles, which enable them to effectively infiltrate the TIME and selectively modulate its key constituents. This paper reviews recent advances in nanoparticle engineering to improve anti‐cancer immunotherapy. Emerging nanoparticle‐based approaches for modulating immune cells, tumor stroma, cytokines and immune checkpoints are discussed, aiming to overcome current challenges in the clinic. In addition, integrating immunotherapy with various treatment modalities such as chemotherapy and photodynamic therapy can be facilitated through the utilization of nanoparticles, thereby enhancing the efficacy of cancer treatment. The future challenges and opportunities of using nanomaterials to reeducate the suppressive immune microenvironment of tumors are also discussed, with the aim of anticipating further advancements in this growing field. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor T‐cell (CAR‐T) therapy is becoming an effective technique for the treatment of patients with relapsed/refractory hematologic malignancies. After analyzing patients with tumor progression and sustained remission after CAR‐T cell therapy, many factors were found to be associated with the efficacy of CAR‐T therapy. This paper reviews the factors affecting the effect of CAR‐T such as tumor characteristics, tumor microenvironment and immune function of patients, CAR‐T cell structure, construction method and in vivo expansion values, lymphodepletion chemotherapy, and previous treatment, and provides a preliminary outlook on the corresponding therapeutic strategies. [ABSTRACT FROM AUTHOR]

Immunotherapy using immune checkpoint inhibitors (ICIs) has shown superior efficacy compared with conventional chemotherapy in certain cancer types, establishing immunotherapy as the fourth standard treatment alongside surgical intervention, chemotherapy, and radiotherapy. In cancer immunotherapy employing ICIs, CD8‐positive cytotoxic T lymphocytes are recognized as the primary effector cells. For effective clinical outcomes, it is essential that the targeted cancer cells express HLA class I molecules to present antigenic peptides derived from the tumor. However, cancer cells utilize various mechanisms to downregulate or lose HLA class I molecules from their surface, resulting in evasion from immune surveillance. Correlations between prognosis and the integrity of HLA class I molecules expressed by cancer cells have been consistently found across different types of cancer. This paper provides an overview of the regulatory mechanisms of HLA class I molecules and their role in cancer immunotherapy, with a particular emphasis on the significance of utilizing pathological tissues to evaluate HLA class I molecules expressed in cancer cells. [ABSTRACT FROM AUTHOR]

Heart diseases remain the primary cause of human mortality in the world. Although conventional therapeutic opportunities fail to halt or recover cardiac fibrosis, the promising clinical results and therapeutic efficacy of engineered chimeric antigen receptor (CAR) T cell therapy show several advancements. However, the current models of CAR‐T cells need further improvement since the T cells are associated with the triggering of excessive inflammatory cytokines that directly affect cardiac functions. Thus, the current study highlights the critical function of heart immune cells in tissue fibrosis and repair. The study also confirms CAR‐T cell as an emerging therapeutic for treating cardiac fibrosis, explores the current roadblocks to CAR‐T cell therapy, and considers future outlooks for research development. Significance statement: The necessity and importance of chimeric antigen receptor (CAR) T cells and their therapeutic efficiency in treating diseases other than cancer, mainly cardiovascular diseases, have emerged in recent years. However, there is still room for advancement in the current models of CAR‐T cell therapy. This paper highlights the evolution and roadblocks of CAR‐T technology at different levels, from technical concerns to clinical outcomes, in an attempt to improve the therapeutic efficiency of CAR‐T cell therapy in this area. [ABSTRACT FROM AUTHOR]

Nanoencapsulation of living cells within artificial shells is a powerful approach for augmenting the inherent capacity of cells and enabling the acquisition of extrinsic functions. However, the current state of the field requires the development of nanoshells that can dynamically sense and adapt to environmental changes by undergoing transformations in form and composition. This paper reports the compositional transformation of an enzyme‐embedded nanoshell of Fe3+‐trimesic acid complex to an iron phosphate shell in phosphate‐containing media. The cytocompatible transformation allows the nanoshells to release functional molecules without loss of activities and biorecognition, while preserving the initial shell properties, such as cytoprotection. Demonstrations include the lysis and killing of Escherichia coli by lysozyme, and the secretion of interleukin‐2 by Jurkat T cells in response to paracrine stimulation by antibodies. This work on micrometric Transformers will benefit the creation of cell‐in‐shell nanobiohybrids that can interact with their surroundings in active and adaptive ways. [ABSTRACT FROM AUTHOR]

Background: It has been reported that programmed death‐ligand 1 (PD‐L1) is highly expressed in cells during viral infection, which helps the virus escape host immunity. However, the relationship between human papillomavirus (HPV) and PD‐L1 in condyloma acuminatum and whether they participate in immunosuppression have not been reported. In this paper, we aimed to explore the expression and significance of PD‐L1 in condyloma acuminatum. Methods: The expression of PD‐L1 in the wart of condyloma acuminatum patients and the foreskin of healthy individuals was evaluated. Lentivirus transfection was used to introduce the HPV11‐E7 gene into HaCaT cells to investigate whether HPV infection could affect the expression of PD‐L1. The successfully constructed HPV11‐E7 HaCaT cells were cocultured with Jurkat cells, and Jurkat cell apoptosis and proliferation as well as the Jurkat cell cycle were evaluated by flow cytometry and cell counting kit‐8 (CCK‐8) assays. Results: PD‐L1 was highly expressed in keratinocytes of genital warts. Through the construction of a cell model, we found that HPV11‐E7 could upregulate the expression of PD‐L1 in HaCaT cells. Furthermore, HPV11‐E7 HaCaT cells can promote the apoptosis of Jurkat cells, inhibit the proliferation of Jurkat cells and mediate the cell cycle arrest of Jurkat cells through the PD‐1/PD‐L1 signalling pathway. Conclusions: HPV infection may upregulate PD‐L1 expression in the keratinocytes of genital warts and participate in the inhibition of local T‐cell function. [ABSTRACT FROM AUTHOR]

Major histocompatibility complex (MHC) genes (referred to as human leukocyte antigen or HLA in humans) are a key component of vertebrate immune systems, coding for proteins which present antigens to T‐cells. These genes are outstanding in their degree of polymorphism, with important consequences for human and animal health. The polymorphism is thought to arise from selection pressures imposed by pathogens on MHC allomorphs, which differ in their antigen‐binding capacity. However, the existing theory has not considered MHC selection in relation to the formation of immune memory. In this paper, we argue that this omission limits our understanding of the evolution of MHC polymorphism and its role in disease. We review recent evidence that has emerged from the massive research effort related to the SARS‐CoV‐2 pandemics, and which provides new evidence for the role of MHC in shaping immune memory. We then discuss why the inclusion of immune memory within the existing theory may have non‐trivial consequence for our understanding of the evolution of MHC polymorphism. Finally, we will argue that neglecting immune memory hinders our interpretation of empirical findings, and postulate that future studies focusing on pathogen‐driven MHC selection would benefit from stratifying the available data according to the history of infection (and vaccination, if relevant). [ABSTRACT FROM AUTHOR]

Summary: Since the publication in 2017 of the revised 4th Edition of the World Health Organization (WHO) classification of haematolymphoid tumours, here referred to as WHO‐HAEM4, significant clinicopathological, immunophenotypic and molecular advances have been made in the field of lymphomas, contributing to refining the diagnostic criteria of several diseases, upgrading entities previously defined as provisional and identifying new entities. This process has resulted in two recent classification proposals of lymphoid neoplasms: the International Consensus Classification (ICC) and the 5th edition of the WHO classification (WHO‐HAEM5). In this paper, we review and compare the two classifications in terms of diagnostic criteria and entity definition, focusing on T‐cell lymphomas and histiocytic/dendritic cell tumours. Moreover, we update the genetic data of the various pathological entities. The main goal is to provide a tool to facilitate the work of the pathologists, haematologists and researchers involved in the diagnosis and treatment of these haematological malignancies. [ABSTRACT FROM AUTHOR]

Summary: A subset of individuals with 'primary' or 'idiopathic' immune thrombocytopenia (ITP) who fail to respond to conventional first‐ and second‐line agents or who lose responsiveness are considered to have 'refractory' disease (rITP), placing them at increased risk of bleeding and complications of intensive treatment. However, the criteria used to define the refractory state vary among studies, which complicates research and clinical investigation. Moreover, it is unclear whether rITP is simply 'more severe' ITP, or if there are specific pathogenic pathways that are more likely to result in refractory disease, and whether the presence or development of rITP can be established or anticipated based on these differences. This paper reviews potential biological features that may be associated with rITP, including genetic and epigenetic risk factors, dysregulation of T cells and cytokine networks, antibody affinity and specificity, activation of complement, impaired platelet production and alterations in platelet viability and clearance. These findings indicate the need for longitudinal studies using novel clinically available methodologies to identify and monitor pathogenic T cells, platelet antibodies and other clues to the development of refractory disease. [ABSTRACT FROM AUTHOR]

Summary: Since its first description by Evans in 1951, this syndrome has been linked to chronic immune thrombocytopenia with the concurrent or delayed onset of autoimmune haemolytic anaemia or neutropenia. For decades, the evolution of Evans syndrome (ES) has carried a poor prognosis and often resulted in chronic steroid exposure, multiple immune suppressing medications directed against T or B lymphocytes, and splenectomy. This paper presents a new view of ES based on recent advances in genomics which begin to classify patients based on their underlying molecular variants in previously described primary immune disorders. This has opened up new avenues of targeted therapy or bone marrow transplant at rather than broad long‐term immune suppression or splenectomy. Importantly, recent studies of the full lifespan of ES suggest that at least 80% of those paediatric patients will progress to various clinical or biological immunopathological manifestations with age despite the resolution of their cytopenias. Those patients merit long‐term follow‐up and monitoring in dedicated transition programs to improve outcome at the adult age. [ABSTRACT FROM AUTHOR]

In this paper, we introduce a numerical and analytical study of the HIV‐1 infection of CD4+ T‐cells conformable fractional mathematical model. This model is studied analytically by Kudryashov and modified Kudryashov methods and numerically by finite difference method. A comparison between the results of the analytical and numerical methods is investigated. We also give some figures that show how accurate the solutions will be obtained from analytical and numerical methods. [ABSTRACT FROM AUTHOR]

This paper is concerned with level‐dependent quasi‐birth‐death (LD‐QBD) processes, i.e., multi‐variate Markov chains with a block‐tridiagonal q$$ q $$‐matrix, and a more general class of block‐structured Markov chains, which can be seen as LD‐QBD processes with total catastrophes. Arguments from univariate birth‐death processes are combined with existing matrix‐analytic formulations to obtain sufficient conditions for these block‐structured processes to be regular, positive recurrent, and absorbed with certainty in a finite mean time. Specifically, it is our purpose to show that, as is the case for competition processes, these sufficient conditions are inherently linked to a suitably defined birth‐death process. Our results are exemplified with two Markov chain models: a study of target cells and viral dynamics and one of kinetic proof‐reading in T cell receptor signal transduction. [ABSTRACT FROM AUTHOR]

Pulmonary fibrosis involves various types of immune cells and soluble mediators, including TGF‐β and IL‐35, a recently identified heterodimeric cytokine that belongs to the IL‐12 cytokine family. However, the effect of regulatory IL‐35 may play an important role in fibrotic diseases. The aim of this paper is to explore the immunoregulatory role of IL‐35 in the development of fibrosis in interstitial lung disease (ILD). To gain a better understanding of this issue, the concentrations of IL‐35 and different profibrotic cytokines in fibrotic (F‐ILD) and non‐fibrotic (NF‐ILD) patients by ELISA were compared to that of intracellular IL‐35 and IL‐17 on CD4+ T cells stimulated in the presence of BAL or with different ratios of recombinant IL‐35 (rIL‐35) and TGF‐β (rTGF‐β), which were evaluated by flow cytometry. We observed that BAL concentration of IL‐35 was lower in F patients (p < 0.001) and was negatively correlated with concentrations of TGF‐β (p < 0.001) and IL‐17 (p < 0.001). In supplemented cell cultures, BAL from NF but not F patients enhanced the percentage of IL‐35 + CD4+ T (p < 0.001) cells and decreased the percentage of IL‐17 + CD4+ T cells (p < 0.001). The percentage of IL‐35 + CD4+ T cells correlated positively with BAL concentration of IL‐35 (p = 0.02), but correlated negatively with BAL concentrations of IL‐17 (p = 0.007) and TGF‐β (p = 0.01). After adjusting the concentrations of recombinant cytokines to establish a TGF‐β: IL‐35 ratio of 1:4, an enhanced percentage of IL‐35 + CD4+ T cells (p < 0.001) but a decreased percentage of IL‐17 + CD4+ T cells (p < 0.001) was observed. After adding recombinant IL‐35 to the BAL from F patients until a 1:4 ratio of TGF‐β: IL‐35 was reached, a significantly increased percentage of IL‐35 + CD4+ T cells (p < 0.001) and a decreased percentage of IL‐17 + CD4+ T cells (p = 0.003) was found. These results suggest that IL‐35 may induce an anti‐fibrotic response, regulating the effect of TGF‐β and the inflammatory response on CD4+ T cells. In addition, the TGF‐β: IL‐35 ratio in BAL has been shown to be a potential biomarker to predict the outcome of F patients with ILD. [ABSTRACT FROM AUTHOR]

The UVB irradiation is well known for its impact on the development of skin cancer. However, low UVB irradiation plays a protective role against various human diseases including cancer through its effect on tumor suppression. This article summarizes the key findings of the paper by Park et al., which describes a novel molecular mechanism of moderate UVB irradiation in suppressing the growth of melanoma and colorectal cancer. Key observations in this article are that moderate UVB irradiation can enhance tumor immunity by (1) increased infiltration of CD4+ and CD8+ T cells; (2) increased infiltration of CD103+ conventional type 1 dendritic cells (cDC1); and (3) a significant decrease of M2 tumor associate macrophages (TAMs) into the tumor. The authors further identified the role of Batf3 transcription factor in moderate UVB irradiation‐mediated anti‐tumor immune response. Deletion of Batf3 transcription factor reversed the tumor suppressive effect with decreased CD103+ cDC1 cell infiltration. This pre‐clinical study provides a very novel mechanistic insight into the utilization of moderate UVB irradiation for the management of melanoma and colorectal cancer. This study further provides the direction of new future research to explore moderate UVB irradiation in combination with checkpoint blockade antibodies to enhance immunotherapeutic response against various solid tumors. [ABSTRACT FROM AUTHOR]

Objectives: This paper reviews current and emerging therapies for multiple myeloma (MM). Methods: Narrative review. Results: MM is a complex, heterogenous condition, and in recent years there has been an expansion in the number and range of treatments. Several new treatment approaches, including enhanced monoclonal antibodies, antibody‐drug conjugates, bispecific T‐cell engagers, and chimeric antigen‐T‐cell therapy are under development. Conclusions: The emergence of new treatments that aim to tackle MM‐associated immune dysfunction has led to improvements in overall survival. [ABSTRACT FROM AUTHOR]

CD247, which is also known as CD3ζ, CD3H, CD3Q, CD3Z, IMD25, T3Z and TCRZ, encodes CD3ζ protein, which is expressed primarily in natural killer (NK) and T cells. Since the discovery of the ζ peptide in 1986, it has been continuously investigated. In this paper, we review the composition, molecular mechanisms and regulatory factors of CD247 expression in T cells; and review the autoimmune diseases, tumours and inflammatory diseases associated with CD247, providing a detailed and comprehensive reference for further research on the mechanism of CD247 and related diseases. [ABSTRACT FROM AUTHOR]

In this paper, using the methods of killing tumors and impulsive differential equations, two immunotherapy antitumor models for describing therapies of general tumors and advanced solid tumors are established. By using the theories of impulsive equations, small amplitude perturbation techniques, and the comparison technique, we obtain the conditions which guarantee the global asymptotical stability of the tumor‐eliminated periodic solution and system permanence, when immunotherapy alone is performed. The numerical results of the influences of the impulsive perturbation on the inherent oscillation show rich dynamics, such as period‐doubling bifurcation and chaos. Moreover, the effects of the combination of radiotherapy with immunotherapy on antitumor are obtained, including the threshold value of stability conditions of tumor‐eradication periodic solution when the mixed combination treatment of immunotherapy and radiotherapy is performed. Some numerical simulations for the effects of the timing of radiotherapy application and the timing of injection T cells on the threshold value are performed. Finally, we present some theoretical methods for suppressing the growth of tumors. [ABSTRACT FROM AUTHOR]

In this paper, we formulate a within‐host dynamics model for HIV/HTLV‐I co‐infection under the influence of cytotoxic T lymphocytes (CTLs). The model incorporates silent HIV‐infected CD4+T cells and silent HTLV‐infected CD4+T cells. The model includes two routes of HIV transmission, virus to cell (VTC) and cell to cell (CTC). It also incorporates two modes of HTLV‐I transmission, horizontal transmission via direct CTC contact and vertical transmission through mitotic division of Tax‐expressing HTLV‐infected cells. The model takes into account five types of distributed‐time delays. We analyze the model by proving the nonnegativity and boundedness of the solutions, calculating all possible equilibria, deriving a set of key threshold parameters, and proving the global stability of all equilibria. The global asymptotic stability of all equilibria is established by utilizing Lyapunov function and LaSalle's invariance principle. We present numerical simulations to justify the applicability and effectiveness of the theoretical results. In addition, we discuss the effect of HTLV‐I infection on the HIV dynamics and vice versa. [ABSTRACT FROM AUTHOR]

In this paper, the dynamics of stochastic human T‐cell leukemia virus type I (HTLV‐I) infection model with cytotoxic T lymphocyte (CTL) immune response is investigated. First, we show that the stochastic model exists as a unique positive global solution originating from the positive initial value. Second, we demonstrate that the stochastic model is stochastically permanent and stochastically ultimately bounded for any positive initial value. Third, we establish sufficient conditions for the existence of ergodic stationary distribution of the stochastic model. Fourth, the threshold R0∗ between extinction and persistence of the virus is obtained. Finally, numerical simulations are carried out to illustrate the theoretical results. [ABSTRACT FROM AUTHOR]

A two‐dimensional tumor‐immune model with the time delay of the adaptive immune response is considered in this paper. The model is designed to account for the interaction between cytotoxic T lymphocytes (CTLs) and cancer cells on the surface of a solid tumor. The model considers the surface growth as a major growth pattern of solid tumors in order to describe the existence of necrotic kernels. The qualitative analysis shows that the immune‐free equilibrium is unstable, and the behavior of positive equilibrium is closely related to the ratio of the immune killing rate to tumor volume growth rate. The positive equilibrium is locally asymptotically stable when the ratio is smaller than a critical value. Otherwise, the occurrence of the delay‐driven Hopf bifurcation at the positive equilibrium is proved. Applying the center manifold reduction and normal form method, we obtain explicit formulas to determine the properties of the Hopf bifurcation. The global continuation of a local Hopf bifurcation is investigated based on the coincidence degree theory. The results reveal that the time of the adaptive immune system taken to response to tumors can lead to oscillation dynamics. We also carry out detailed numerical analysis for parameters and numerical simulations to illustrate our qualitative analysis. Numerically, we find that shorter immune response time can lead to longer patient survival time, and the period and amplitude of a stable periodic solution increase with the increasing immune response time. When CTLs recruitment rate and death rate vary, we show how the ratio of the immune killing rate to tumor volume growth rate and the first bifurcation value change numerically, which yields further insights to the tumor‐immune dynamics. [ABSTRACT FROM AUTHOR]

Summary: Prolonged cytopenia after CAR‐T cell therapy is an acknowledged problem. At present, the causes and implications of prolonged cytopenia are unclear. The paper by Kitamura et al identified that prolonged cytopenia is associated with alterations in the bone marrow niche identified before CAR‐T therapy, indicating a potential predictor of this serious side‐effect of treatment. Commentary on: Kitamura et al. Bone marrow microenvironment disruption and sustained inflammation with prolonged haematologic toxicity after CAR T‐cell therapy? Br J Haematol 2023;202:294‐307. [ABSTRACT FROM AUTHOR]