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The International Journal of Molecular Sciences has published a special issue on molecular oncology, featuring nineteen articles written by leading experts in specific cancer research fields. The articles cover a wide range of topics, including cancer development, progression, and treatment options. Some of the areas explored include endoplasmic reticulum stress activation, immunotherapies, non-genetic determinants of cancer, environmental carcinogens, social stress, epigenetic reprogramming, drug resistance, microbiome modulation, tumor microenvironment, and the efficacy of ALK inhibitors. The issue also discusses the use of liposomes as a delivery strategy for chemotherapeutic drugs. The articles provide valuable insights into the global burden of cancer and offer potential avenues for further research and improved treatment options. The editorial expresses gratitude to the authors, reviewers, and editors for their contributions and hopes that the articles will promote further research in cancer treatment. [Extracted from the article]

A time-delayed virus dynamic model is proposed with general monotonic incidence, different nonlinear CTL (cytotoxic T lymphocyte) responses [CTL elimination function p y g 1 (z) and CTL stimulation function c y g 2 (z) ], and immune impairment. Indeed, the different CTL responses pose challenges in obtaining the dissipativeness of the model. By constructing appropriate Lyapunov functionals with some detailed analysis techniques, the global stability results of all equilibria of the model are obtained. By the way, we point out that the partial derivative f v (x , 0) is increasing (but not necessarily strictly) in x > 0 for the general monotonic incidence f (x , v). However, some papers defaulted that the partial derivative was strictly increasing. Our main results show that if the basic reproduction number R 0 ≤ 1 , the infection-free equilibrium E 0 is globally asymptotically stable (GAS); if CTL stimulation function c y g 2 (z) = 0 for z = 0 and the CTL threshold parameter R 1 ≤ 1 < R 0 , then the immunity-inactivated infection equilibrium E 1 is GAS; if the immunity-activated infection equilibrium E + exists, then it is GAS. Two specific examples are provided to illustrate the applicability of the main results. The main results acquired in this paper improve or extend some of the existing results. [ABSTRACT FROM AUTHOR]

As the prevalence of viral infection in body, human T‐cell leukemia virus type 1 (HTLV‐1) is receiving increasing attention. Research on the corresponding virus models is of great significance to tackle the challenges of understanding HTLV‐1 development and treatment. This paper focuses on the dynamic analysis for a stochastic model with nonlinear cytotoxic T lymphocyte (CTL) response, which is driven by Ornstein–Uhlenbeck (OU) process to model the progression of HTLV‐1 in vivo. Rich dynamic behaviors such as the extinction of infected CD4+ T cells (ITCs), stationary distribution (SD), probability density, and finite‐time stability (FTS) of the model are established to reveal the interaction of cell populations. The optimal therapeutic strategy based on the cost‐benefit viewpoint is further obtained. Finally, illustrative numerical simulations are represented to corroborate the effectiveness of treatment and the ambient perturbation's impact that strengthening the noise strength can lead to rapid virus clearance. [ABSTRACT FROM AUTHOR]

This paper explores the dynamics analysis of a human immunodeficiency virus (HIV) model with saturated cytotoxic T lymphocyte (CTL) immune response and Beddington–DeAngelis infection rate. There are two time delays in the model to describe the time needed for infection of cell and CTL immune response generation, respectively. We obtain two thresholds and three possible equilibria from the model. By analyzing the corresponding characteristic equations, we study the stabilities of equilibrium and the effect of delays on CTL immune response. The results indicate that when immune delay is present, the steady state of equilibrium is disrupted and leads to a Hopf bifurcation. Finally, we use sensitivity analyses to show the effect of parameters on thresholds and numerical simulations to illustrate the theoretical results. [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]

This paper develops a mathematical model to investigate the Human Immunodeficiency Virus (HIV) infection dynamics. The model includes two transmission modes (cell-to-cell and cell-free), two adaptive immune responses (cytotoxic T-lymphocyte (CTL) and antibody), a saturated CTL immune response, and latent HIV infection. The existence and local stability of equilibria are fully characterized by four reproduction numbers. Through sensitivity analyses, we assess the partial rank correlation coefficients of these reproduction numbers and identify that the infection rate via cell-to-cell transmission, the number of new viruses produced by each infected cell during its life cycle, the clearance rate of free virions, and immune parameters have the greatest impact on the reproduction numbers. Additionally, we compare the effects of immune stimulation and cell-to-cell spread on the model's dynamics. The findings highlight the significance of adaptive immune responses in increasing the population of uninfected cells and reducing the numbers of latent cells, infected cells, and viruses. Furthermore, cell-to-cell transmission is identified as a facilitator of HIV transmission. The analytical and numerical results presented in this study contribute to a better understanding of HIV dynamics and can potentially aid in improving HIV management strategies. [ABSTRACT FROM AUTHOR]

Photothermal therapy (PTT) is a cancer-targeted treatment approach.The occurrence of tumors may be related to microbial infections (Viruses, bacteria, fungi, etc.), which probably provokes anti-tumor immunity. However, T cells in the context of cancer become exhausted and dysfunctional. Galectin-9 (Gal-9) is highly expressed in normal tissues and associates with body immune tolerance, and was firstly evidenced with much higher expression on the primary solid tumors than CD80/86 (B7) and CD274 (PD-L1) here, which suggests that Gal-9 may be a key factor in inhibiting the anti-tumor immunity, and its receptor T cell immunoglobulin and mucin domain 3 (TIM-3) was discovered on the cytotoxic T lymphocytes (CTL) with high expression as well based on the single cell analysis. The immune checkpoint communications showed that the Gal-9/TIM-3 axis played the most vital role on negatively regulating the anti-tumor immunity of CTL for melanoma. Then, we used a novel transdermal photothermal nanosensitizer (FSGG) loading Gal-9 siRNA (FSGG/siGal-9) for knocking the tumor cells down Gal-9 to block the Gal-9/TIM-3 axis and prohibit CTL exhaustion synergizing PTT against melanoma, which evidenced good effects on inhibiting tumor growth and enhancing anti-tumor immunity, named "photothermal immunotherapy". This paper provides a new perspective for tumor prevention and treatment. This study explores the synergistic effects of photothermal therapy and silencing Gal-9 to achieve photothermal immunotherapy treating melanoma with an integrated FSGG nanostructure. [ABSTRACT FROM AUTHOR]

Tumor immune escape refers to the inability of the immune system to clear tumor cells, which is one of the major obstacles in designing effective treatment schemes for cancer diseases. Although clinical studies have led to promising treatment outcomes, it is imperative to design theoretical models to investigate the long-term treatment effects. In this paper, we develop a mathematical model to study the interactions among tumor cells, immune escape tumor cells, and T lymphocyte. The chimeric antigen receptor (CAR) T-cell therapy is also described by the mathematical model. Bifurcation analysis shows that there exists backward bifurcation and saddle-node bifurcation when the immune intensity is used as the bifurcation parameter. The proposed model also exhibits bistability when its parameters are located between the saddle-node threshold and backward bifurcation threshold. Sensitivity analysis is performed to illustrate the effects of different mechanisms on the backward bifurcation threshold and basic immune reproduction number. Simulation studies confirm the bifurcation analysis results and predict various types of treatment outcomes using different CAR T-cell therapy strengths. Analysis and simulation results show that the immune intensity can be used to control the tumor size, but it has no effect on the control of the immune escape tumor size. The introduction of the CAR T-cell therapy will reduce the immune escape tumor size and the treatment effect depends on the CAR T-cell therapy strength. [ABSTRACT FROM AUTHOR]

Efforts to treat cancer using chimeric antigen receptor (CAR)-T therapy have made astonishing progress and clinical trials against hematopoietic malignancies have demonstrated their use. However, there are still disadvantages which need to be addressed: high costs, and side effects such as Graft-versus-Host Disease (GvHD) and Cytokine Release Syndrome (CRS). Therefore, recent efforts have been made to harness the properties of certain immune cells to treat cancer—not just T cells, but also natural killer (NK) cells, macrophages (Mφ), dendritic cells (DC), etc. In this paper, we will introduce immune cell-based cellular therapies that use various immune cells and describe their characteristics and their clinical situation. The development of immune cell-based cancer therapy fully utilizing the unique advantages of each and every immune cell is expected to enhance the survival of tumor patients owing to their high efficiency and fewer side effects. [ABSTRACT FROM AUTHOR]

Simple Summary: Cell therapy is emerging as a promising modality to treat cancers such as hematological malignancies and solid tumors; hence there is a need to develop processes to manufacture and maintain functional and lasting cells. The use of cytokines, as well as transcription and growth factors, is critical to ensure effective cell therapeutics. This is especially important for allogeneic cell therapies that employ induced pluripotent stem cells (iPSC). The use of iPSC offers the potential to treat a large number of patients with consistent material without relying on limited donor cells and the delay associated with processing immediately before treatment. This paper demonstrates the importance and use of cytokines and growth factors in driving the iPSC-to-effector differentiation and expansion process, which leads to the generation of functional and persistent immune-effector cells such as natural killer cells or T cells. Cytokines and other growth factors are essential for cell expansion, health, function, and immune stimulation. Stem cells have the additional reliance on these factors to direct differentiation to the appropriate terminal cell type. Successful manufacturing of allogeneic cell therapies from induced pluripotent stem cells (iPSCs) requires close attention to the selection and control of cytokines and factors used throughout the manufacturing process, as well as after administration to the patient. This paper employs iPSC-derived natural killer cell/T cell therapeutics to illustrate the use of cytokines, growth factors, and transcription factors at different stages of the manufacturing process, ranging from the generation of iPSCs to controlling of iPSC differentiation into immune-effector cells through the support of cell therapy after patient administration. [ABSTRACT FROM AUTHOR]

In this paper, we incorporate immune systems containing Cytotoxic T lymphocyte and humoral immunity into a general human immunodeficiency viruses infection model, which also considers logistic growth for target cells and both modes of spread, cell-to-cell and cell-free represents, by linear functions. We derive five threshold parameters which are used to study the existence of equilibria. By considering the characteristic equations, the local stability of disease-free and immune-free equilibria is investigated. Lyapunov functions and LaSalle's invariance are constructed to prove the global stability of all steady states. Global dynamics of the human immunodeficiency viruses model can be accurately expressed by threshold parameters; also the existence of Hopf bifurcation is discussed and the results are expressed in the form of a proposition. Furthermore, numerical simulations confirm the corresponding theoretical results. [ABSTRACT FROM AUTHOR]

Breast cancer ranks among the most prevalent malignancies affecting the female population and is a prominent contributor to cancer-related mortality. Mathematical modeling is a significant tool that can be employed to comprehend the dynamics of breast cancer progression and dissemination and to formulate novel therapeutic approaches. This paper introduces a mathematical model of breast cancer that utilizes the Caputo–Fabrizio fractal-fractional derivative. The aim is to elucidate and comprehend the intricate dynamics governing breast cancer cells and cytotoxic T lymphocytes in the context of the fractional derivative. The derivative presented herein offers a broader perspective than the conventional derivative, as it incorporates the intricate fractal characteristics inherent in the process of tumor proliferation. The significance of this study lies in its contribution to a novel mathematical model for breast cancer, which incorporates the fractal characteristics of tumor development. The present model possesses the capability to investigate the impacts of diverse treatment strategies on the proliferation of breast cancer, as well as to formulate novel treatment strategies that exhibit enhanced efficacy. [ABSTRACT FROM AUTHOR]

This paper formulates and analyzes two mathematical models that describe the within-host dynamics of human immunodeficiency virus type 1 (HIV-1) with impairment of both cytotoxic T lymphocytes (CTLs) and B cells. Both viral transmission (VT) and cellular infection (CT) mechanisms are considered. The second model is a generalization of the first model that includes distributed time delays. For the two models, we establish the non-negativity and boundedness of the solutions, find the basic reproductive numbers, determine all possible steady states and establish the global asymptotic stability properties of all steady states by means of the Lyapunov method. We confirm the theoretical results by conducting numerical simulations. We conduct a sensitivity analysis to show the effect of the values of the parameters on the basic reproductive number. We discuss the results, showing that impaired B cells and CTLs, time delay and latent CT have significant effects on the HIV-1 dynamics. [ABSTRACT FROM AUTHOR]

Vitiligo is caused by an autoimmune reaction against melanocytes leading to melanocyte loss. The cause of vitiligo is an interaction between genetic susceptibility and environmental factors. Both the adaptive immune system—through cytotoxic CD8+ T cells and melanocyte specific antibodies—and the innate immune system are involved in these immune processes in vitiligo. While recent data stressed the importance of innate immunity in vitiligo, the question remains why vitiligo patients' immune response becomes overly activated. Could a long‐term increase in innate memory function, described as trained immunity after vaccination and in other inflammatory diseases, play a role as an enhancer and continuous trigger in the pathogenesis of vitiligo? After exposure to certain stimuli, innate immune system is able to show an enhanced immunological response to a secondary trigger, indicating a memory function of the innate immune system, a concept termed trained immunity. Trained immunity is regulated by epigenetic reprogramming, including histone chemical modifications and changes in chromatin accessibility that cause sustained changes in the transcription of specific genes. In responses to an infection, trained immunity is beneficial. However, there are indications of a pathogenic role of trained immunity in inflammatory and autoimmune diseases, with monocytes presenting features of a trained phenotype, resulting in increased cytokine production, altered cell metabolism through mTOR signaling, and epigenetic modifications. This hypothesis paper focusses on vitiligo studies that have shown these indications, suggesting the involvement of trained immunity in vitiligo. Future studies focusing on metabolic and epigenetic changes in innate immune cell populations in vitiligo could help in elucidating the potential role of trained immunity in vitiligo pathogenesis. [ABSTRACT FROM AUTHOR]

This paper presents and analyzes two mathematical models for the human immunodeficiency virus type-1 (HIV-1) infection with Cytotoxic T Lymphocyte cell (CTL) immune impairment. These models describe the interactions between healthy CD 4 + T cells, latently and actively infected cells, HIV-1 particles, and CTLs. The healthy CD 4 + T cells might be infected when they make contact with: (i) HIV-1 particles due to virus-to-cell (VTC) contact; (ii) latently infected cells due to latent cell-to-cell (CTC) contact; and (iii) actively infected cells due to active CTC contact. Distributed time delays are considered in the second model. We show the nonnegativity and boundedness of the solutions of the systems. Further, we derive basic reproduction numbers ℜ 0 and ℜ ˜ 0 , that determine the existence and stability of equilibria of our proposed systems. We establish the global asymptotic stability of all equilibria by using the Lyapunov method together with LaSalle's invariance principle. We confirm the theoretical results by numerical simulations. The effect of immune impairment, time delay and CTC transmission on the HIV-1 dynamics are discussed. It is found that weak immunity contributes significantly to the development of the disease. Further, we have established that the presence of time delay can significantly decrease the basic reproduction number and then suppress the HIV-1 replication. On the other hand, the presence of latent CTC spread increases the basic reproduction number and then enhances the viral progression. Thus, neglecting the latent CTC spread in the HIV-1 infection model will lead to an underestimation of the basic reproduction number. Consequently, the designed drug therapies will not be accurate or sufficient to eradicate the viruses from the body. These findings may help to improve the understanding of the dynamics of HIV-1 within a host. [ABSTRACT FROM AUTHOR]

This document is a first-person interview with Fabrizia Zevolini, the first author of a paper titled "Polo-like kinase 1 regulates immune synapse assembly and cytotoxic T cell function by driving microtubule dynamics." The paper discusses the role of Polo-like kinase 1 (PLK1) in the assembly of the immune synapse, a cell-cell contact that cytotoxic T cells establish with their targets for effective killing. The study found that inhibiting PLK1 suppressed cytotoxic T cell function, highlighting a potential drawback of PLK1-targeted therapies. The author also discusses the challenges faced during the project and their motivation to pursue a career in science. The paper was published in the Journal of Cell Science, a prestigious journal that reaches a broad scientific community. [Extracted from the article]

Graph: hum.2020.29127.cfp figure1.jpg In recent years, there has been significant progress in the development of novel cancer immunotherapies including immune checkpoint blockade (ICB) therapy, chimeric antigen receptor T cells (CAR-T) therapy, adoptive cell mediated therapy, tumor vaccines and the development of bispecific T cell engager (BiTE) antibodies. Novel oncolytic viruses can produce selective tumor cell killing and can be genetically manipulated to induce anti-tumor immune responses that are beneficial in treatment and are non-redundant and even synergistic to other immunotherapies. [Extracted from the article]

This paper addresses the controversy of Granzyme B (GzmB) expression by murine Myeloid Derived Suppressor Cells (MDSCs). MDSCs are a heterogenous immature myeloid population that are generated in chronic inflammatory pathologies for the purpose to suppress inflammatory responses. MDSCs express a multitude of factors to induce suppressive function such as PD-L1, reactive oxygen species (ROS), nitric oxide synthase (iNOS), and Arginase-1. Recently, Dufait et al. sought to demonstrate GzmB as an additional mechanism for suppression by MDSCs. They reported that murine MDSCs not only significantly express GzmB as well as Perforin (Prf1), but this expression is functionally important for tumor growth in vivo as well as tumor migration in vitro. We conducted experiments to address the same question but made confounding observations: MDSCs under stringent developmental process do not express GzmB. Our results show that not only GzmB protein is not produced at functional level, but the mRNA transcript is not detectable either. In fact, the GzmB protein found in the media of MDSC culture was due to T cells or natural killer cells contained in bone marrow and cultured alongside MDSCs. We strengthen this finding by genetically deleting GzmB from the myeloid lineage and measuring tumor burden compared to WT counterpart. Our results show no significant difference in tumor burden, suggesting that even if there is minor expression of GzmB, it is not produced at a functional amount to affect tumor growth. Therefore, this paper proposes alternative theories that align with the known understanding of GzmB expression and secretion. [ABSTRACT FROM AUTHOR]

Natural killer T cells （NKT） are a class of subgroups of T cells with NK cell receptors and T cell receptors that show both the properties of NK cells and T cells. It linked the innate immune response and acquired immune response, restricted identified CD1d-glycolipid antigens, activation quickly secreted a large number of cytokines to regulate the body's immune response. The human liver is rich in NKT cells, so the role of NKT cells in the liver disease aroused widespread interest. This paper summarizes the progress of immunology in the development of NKT cells in liver fibrosis. [ABSTRACT FROM AUTHOR]

In this paper, a reaction–diffusion–chemotaxis HIV-1 model with a cytotoxic T lymphocyte (CTL) immune response and general sensitivity is investigated. We first prove the global classical solvability and L ∞ -boundedness for the considered model in a bounded domain with arbitrary spatial dimensions, which extends the previous existing results. Then, we apply the global existence result to the case with a linear proliferation immune response and an incidence rate. We study the spatiotemporal dynamics about the three types of spatially homogeneous steady states: infection-free steady state S 0 , CTL-inactivated infection steady state S 1 , and CTL-activated infection steady state S ∗. Our analyses indicate that S 0 is globally asymptotically stable if the basic reproduction number R 0 is less than 1; if R 0 is between 1 and a threshold, then S 1 is globally asymptotically stable. However, if R 0 is larger than the threshold, then the chemoattraction and chemorepulsion can destabilize S ∗ , and thus, a spatiotemporal pattern forms as the chemotactic sensitivity crosses certain critical values. We obtain two kinds of important patterns, which are induced by chemotaxis: stationary Turing pattern and irregular oscillatory pattern. We also find that different chemotactic response functions can affect system's dynamics. Based on some empirical parameter values, numerical simulations are given to illustrate the effectiveness of the theoretical predications. [ABSTRACT FROM AUTHOR]

Malignant glioma is an aggressive primary brain tumor. Due to its location, the interactions of glioma and the immune system are complex. We start this paper by proposing a simple mathematical model that describes the interaction among glioma cells, microglia and cytotoxic T lymphocytes (CTLs). The existence and stability conditions of the equilibrium points are analyzed. Numerical results showed that neither microglia nor CTLs has the ability to eradicate the tumor. As a result, we extend the model by including the chemotherapeutic agent. The model has six equilibrium points, and one of these points represents a cured state. Through local stability, we found a range of values for the infusion rate that guarantees the elimination of glioma, as well as preventing the glioma from reoccurring. [ABSTRACT FROM AUTHOR]

In this paper, the dynamical behaviors of a multiple delayed HIV-1 infection model which describes the interactions of humoral, cytotoxic T lymphocyte (CTL) immune responses, and two modes of transmission that are the classical virus-to-cell infection and the direct cell-to-cell transmission are investigated. The model incorporates three delays, including the delays of cell infection, virus production and activation of immune response. We first prove the well-posedness of the model, and calculate the biological existence of equilibria and the reproduction numbers, which contain virus infection, humoral immune response, CTL immune response, CTL immune competition, and humoral immune competition. Further, the threshold conditions for the local and global stability of the equilibria for infection-free, immune-free, antibody response, CTL response, and interior are established by utilizing linearization method and the Lyapunov functionals. The existence of Hopf bifurcation with immune delay as a bifurcation parameter is investigated by using the bifurcation theory. Numerical simulations are carried out to illustrate the theoretical results and reveal the effects of some key parameters on viral dynamics. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19) is a respiratory disease that appeared in 2019 caused by a virus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 is still spreading and causing deaths around the world. There is a real concern of SARS-CoV-2 coinfection with other infectious diseases. Tuberculosis (TB) is a bacterial disease caused by Mycobacterium tuberculosis (Mtb). SARS-CoV-2 coinfection with TB has been recorded in many countries. It has been suggested that the coinfection is associated with severe disease and death. Mathematical modeling is an effective tool that can help understand the dynamics of coinfection between new diseases and well-known diseases. In this paper, we develop an in-host TB and SARS-CoV-2 coinfection model with cytotoxic T lymphocytes (CTLs). The model investigates the interactions between healthy epithelial cells (ECs), latent Mtb-infected ECs, active Mtb-infected ECs, SARS-CoV-2-infected ECs, free Mtb, free SARS-CoV-2, and CTLs. The model's solutions are proved to be nonnegative and bounded. All equilibria with their existence conditions are calculated. Proper Lyapunov functions are selected to examine the global stability of equilibria. Numerical simulations are implemented to verify the theoretical results. It is found that the model has six equilibrium points. These points reflect two states: the mono-infection state where SARS-CoV-2 or TB occurs as a single infection, and the coinfection state where the two infections occur simultaneously. The parameters that control the movement between these states should be tested in order to develop better treatments for TB and COVID-19 coinfected patients. Lymphopenia increases the concentration of SARS-CoV-2 particles and thus can worsen the health status of the coinfected patient. [ABSTRACT FROM AUTHOR]

In this paper, we propose and study a Middle East respiratory syndrome coronavirus (MERS-CoV) infection model with cytotoxic T lymphocyte (CTL) immune response and intracellular delay. This model includes five compartments: uninfected cells, infected cells, viruses, dipeptidyl peptidase 4 (DPP4), and CTL immune cells. We obtained an immunity-inactivated reproduction number R 0 and an immunity-activated reproduction number R 1 . By analyzing the distributions of roots of the corresponding characteristic equations, the local stability results of the infection-free equilibrium, the immunity-inactivated equilibrium, and the immunity-activated equilibrium were obtained. Moreover, by constructing suitable Lyapunov functionals and combining LaSalle's invariance principle and Barbalat's lemma, some sufficient conditions for the global stability of the three types of equilibria were obtained. It was found that the infection-free equilibrium is globally asymptotically stable if R 0 ≤ 1 and unstable if R 0 > 1 ; the immunity-inactivated equilibrium is locally asymptotically stable if R 0 > 1 > R 1 and globally asymptotically stable if R 0 > 1 > R 1 and condition (H1) holds, but unstable if R 1 > 1 ; and the immunity-activated equilibrium is locally asymptotically stable if R 1 > 1 and is globally asymptotically stable if R 1 > 1 and condition (H1) holds. [ABSTRACT FROM AUTHOR]

In the course of reverse transcription, drug-sensitive strain can mutate to a drug-resistant one. Cell-to-cell transmission is proved to be more efficient than virus-to-cell infection. The population of Cytotoxic T Lymphocytes (CTLs) can be divided into CTL precursors and CTL effectors. Naive CTL precursors are those that never have contacted antigen, circulating around the body. Once the host is infected, CTL precursors (CTLp) begin to proliferate and differentiate into CTL effectors (CTLe), which have antiviral activity. In this paper, we study an HIV model with drug-sensitive and drug-resistant mixed strains, CTLp and CTLe, both viral and cellular infections. The basic reproduction ratios for each strain are derived and the stability of each feasible equilibrium is analyzed by using Routh–Hurwitz criteria. The periodic solutions may occur near the equilibrium with CTL immune response via Hopf bifurcation. By using normal form theory, we find more information about the limit cycles, such as the amplitude, phase and stability. [ABSTRACT FROM AUTHOR]

Experimental results on the immune response to cancer indicate that activation of cytotoxic T lymphocytes (CTLs) through interactions with dendritic cells (DCs) can trigger a change in CTL migration patterns. In particular, while CTLs in the pre-activation state move in a non-local search pattern, the search pattern of activated CTLs is more localised. In this paper, we develop a kinetic model for such a switch in CTL migration modes. The model is formulated as a coupled system of balance equations for the one-particle distribution functions of CTLs in the pre-activation state, activated CTLs and DCs. CTL activation is modelled via binary interactions between CTLs in the pre-activation state and DCs. Moreover, cell motion is represented as a velocity-jump process, with the running time of CTLs in the pre-activation state following a long-tailed distribution, which is consistent with a Lévy walk, and the running time of activated CTLs following a Poisson distribution, which corresponds to Brownian motion. We formally show that the macroscopic limit of the model comprises a coupled system of balance equations for the cell densities, whereby activated CTL movement is described via a classical diffusion term, whilst a fractional diffusion term describes the movement of CTLs in the pre-activation state. The modelling approach presented here and its possible generalisations are expected to find applications in the study of the immune response to cancer and in other biological contexts in which switch from non-local to localised migration patterns occurs. [ABSTRACT FROM AUTHOR]

Lichen planus is a chronic disease affecting the skin, appendages, and mucous membranes. A cutaneous lichen planus is a rare disease occurring in less than 1% of the general population, while oral illness is up to five times more prevalent; still, both forms equally impair the patient's quality of life. The etiology of lichen planus is not entirely understood. Yet, immune-mediated mechanisms have been recognized since environmental factors such as hepatitis virus infection, mechanical trauma, psychological stress, or microbiome changes can trigger the disease in genetically susceptible individuals. According to current understanding, lichen planus immunopathogenesis is caused by cell-mediated cytotoxicity, particularly cytotoxic T lymphocytes, whose activity is further influenced by Th1 and IL-23/Th-17 axis. However, other immunocytes and inflammatory pathways complement these mechanisms. This paper presents a comprehensive insight into the actual knowledge about lichen planus, with the causal genetic and environmental factors being discussed, the immunopathogenesis described, and the principal effectors of its inflammatory circuits identified. [ABSTRACT FROM AUTHOR]

In this paper, we study a mathematical model of Hepatitis C Virus (HCV) infection. We present a compartmental mathematical model involving healthy hepatocytes, infected hepatocytes, non-activated dendritic cells, activated dendritic cells and cytotoxic T lymphocytes. The derivative used is of non-local fractional order and with non-singular kernel. The existence and uniqueness of the system is proven and its stability is analyzed. Then, by applying the Laplace Adomian decomposition method for the fractional derivative, we present the semi-analytical solution of the model. Finally, some numerical simulations are performed for concrete values of the parameters and several graphs are plotted to reveal the qualitative properties of the solutions. [ABSTRACT FROM AUTHOR]

In this paper, we derive a delayed epidemic model to describe the characterization of cytotoxic T lymphocyte (CTL)-mediated immune response against virus infection. The stability of equilibria and the existence of Hopf bifurcation are analysed. Theoretical results reveal that if the basic reproductive number is greater than 1, the positive equilibrium may lose its stability and the bifurcated periodic solution occurs when time delay is taken as the bifurcation parameter. Furthermore, we investigate an optimal control problem according to the delayed model based on the available therapy for hepatitis B infection. With the aim of minimizing the infected cells and viral load with consideration for the treatment costs, the optimal solution is discussed analytically. For the case when periodic solution occurs, numerical simulations are performed to suggest the optimal therapeutic strategy and compare the model-predicted consequences. [ABSTRACT FROM AUTHOR]

In this paper, we develop a diffusive and delayed hepatitis B virus (HBV) infection model, which incorporates both virus‐to‐cell and cell‐to‐cell transmissions along with cytotoxic T lymphocyte (CTL) immune response. Two threshold parameters ℜ0$$ {\mathfrak{\Re}}_0 $$ (basic reproduction number) and ℜ1$$ {\mathfrak{\Re}}_1 $$ (immune response reproduction number) are defined, which determine the dynamic behavior of the model. Employing the approach of Lyapunov functionals, we show that the infection‐free steady state is globally asymptotically stable when ℜ0≤1$$ {\mathfrak{\Re}}_0\le 1 $$; the immune‐free infected steady state is globally asymptotically stable when ℜ1≤1<ℜ0$$ {\mathfrak{\Re}}_1\le 1<{\mathfrak{\Re}}_0 $$; and the immune‐present steady state is globally asymptotically stable when ℜ0>1,ℜ1>1$$ {\mathfrak{\Re}}_0>1,{\mathfrak{\Re}}_1>1 $$, and φ(I)=I$$ \varphi (I)=I $$. We perform the sensitivity and uncertainly analysis on ℜ0$$ {\mathfrak{\Re}}_0 $$ with respect to parameters and find that the most important parameter that drives the HBV infection is the mortality of HBV DNA capsids. Moreover, the theoretical results are supported with numerical simulations. [ABSTRACT FROM AUTHOR]

The human immunodeficiency virus (HIV) interacts with the immune cells within the human body, where the environment is uncertain and noisy. Stochastic models can successfully encapsulate the effect of such a noisy environment compared to their deterministic counterparts. The human immune system is complex but well-coordinated with various immune cells like C D 4 + T cells, dendritic cells, and cytotoxic T-lymphocyte (CTL) cells, among many others. The CTL can kill the antigenic cells after its recognition. However, the efficacy of CTL in removing the infected C D 4 + T cells is progressively compromised in HIV-infected individuals. This paper considers a noise-induced HIV-immune cell interaction model with immune impairment. A multiplicative white noise is introduced in the infection rate parameter to represent the fluctuations around the average value of the rate parameter as a causative effect of the noise. We analyzed the deterministic and stochastic models and prescribed sufficient conditions for infection eradication and persistence. It is determined under what parametric restrictions the asymptotic solutions of the noise-induced system will be a limiting case of the deterministic solutions. Simulation results revealed that the solutions of the deterministic system either converge to a CTL-dominated interior equilibrium or a CTL-free immunodeficient equilibrium, depending on the initial values of the system. Stochastic analysis divulged that higher noise might be helpful in the infection removal process. The extinction time of infected C D 4 + T cells for some fixed immune impairment gradually decreases with increasing noise intensity and follows the power law. [ABSTRACT FROM AUTHOR]

Caspase-3 is generally considered to be the most important terminal shear enzyme in the process of apoptosis, as well as an important part of cytotoxic T lymphocytes (CTL) killing mechanism, which is confirmed to play an important role in vertebrate cell apoptosis and immune system, and is poorly reported in invertebrates. In this paper, we used bioinformatics to perform amino acid multiple sequence alignment and protein structural domain analysis, and constructed a phylogenetic tree to identify the full-length cDNA of the cloned caspase-3 of Cristaria plicata (Named CpCaspase-3). The expression of caspase-1, caspase-7, caspase-8, and caspase-9 was found to be down-regulated by double-stranded RNA interference of CpCaspase-3 in C. plicata. Some degree of disruption of the caspase signaling pathway occurs. The expression of CpCaspase-3 was affected after injection of Lipopolysaccharide (LPS), Peptidoglycan (PGN), polyinosinic-polycytidylic acid (poly(I:C)), and Aeromonas hydrophila. These results were suggested that CpCaspase-3 was involved in the immune response of C. plicata. The wound recovery process of C. plicata was simulated and CpCaspase-3 was found to promote wound recovery. An autophagy inhibition and autophagy activation model of mussels was constructed, where apoptosis and autophagy undergo crosstalk, and inhibition of autophagy induces the onset of apoptosis, and similarly autophagy activation inhibits the process of apoptosis instead. In addition, a recombinant CpCaspase-3-pEGFP-C1 plasmid was constructed for subcellular localization experiments and found that CpCaspase-3 was distributed in both the nucleus and the cytoplasm. This paper aims to unveil the immune mechanism of C. plicata and provide a theoretical basis for the healthy culture of shellfish. • It was demonstrated that CpCaspase-3 plays a key role in the wound healing process of Cristaria plicata. • A negative correlation between autophagy and apoptosis in the Cristaria plicata was revealed. • It was revealed that microcystin increased the complexity of the crosstalk between autophagy and apoptosis. [ABSTRACT FROM AUTHOR]

In this Q&A, Cell Press Community Review Scientific Editor Leia Judge talks to Dr. Clint Allen and Dr. Sandro Santagata about their new papers "Phenotypic plasticity and reduced tissue retention of exhausted tumor-infiltrating T cells following neoadjuvant immunotherapy in head and neck cancer" and "Lymphocyte networks are dynamic cellular communities in the immunoregulatory landscape of lung adenocarcinoma" and their experiences with publishing through Cell Press Community Review. [ABSTRACT FROM AUTHOR]

The Latvian research results show that patients with CFS/ME are not a risk group for COVID-19; however, COVID-19 causes symptoms similar to CFS/ME. Chronic fatigue syndrome, or myalgic encephalomyelitis (CFS/ME), is a debilitating disease with unknown causes that is more common in women and tends to develop between patients' mid-20s and mid-40s. This Special Issue on CFS/ME collects 18 papers with an interdisciplinary view on the current demographic and epidemiological data and immunological characteristics of CFS/ME and examines the different pathogenic hypotheses, as well as giving information about the latest knowledge on diagnostic investigations, pharmacological, integrative, physical, cognitive-behavioral and psychological curative approaches. 10.3390/jcm10204786 21 Mckay P.G., Walker H., Martin C.R., Fleming M. Exploratory study into the relationship between the symptoms of chronic fatigue syndrome (CFS)/myalgic encephalomyelitis (ME) and fibromyalgia (FM) using a quasiexperimental design. [Extracted from the article]

T-cell intracellular antigen 1 (TIA1)-related/like (TIAR/TIAL1) protein is a multifunctional RNA-binding protein (RBP) involved in regulating many aspects of gene expression, independently or in combination with its paralog TIA1. TIAR was first described in 1992 by Paul Anderson's lab in relation to the development of a cell death phenotype in immune system cells, as it possesses nucleolytic activity against cytotoxic lymphocyte target cells. Similar to TIA1, it is characterized by a subcellular nucleo-cytoplasmic localization and ubiquitous expression in the cells of different tissues of higher organisms. In this paper, we review the relevant structural and functional information available about TIAR from a triple perspective (molecular, cellular and pathophysiological), paying special attention to its expression and regulation in cellular events and processes linked to human pathophysiology. [ABSTRACT FROM AUTHOR]

α-Galactosyl ceramide (GalCer) as a glycolipid has been long used as a standard reference for positive control in natural killer T cell studies. The (1,2)-disaccharide analogue of GalCer attracts a special attention in the study of lysosomal glycolipid processing. This paper describes the synthesis and self-assembly behaviors of GalCer 1,2-polysaccharide analogue (PolyGalCer), having considered the 1,2-disaccharide analogue as a structural motif. The synthesis of PolyGalCer is performed via one-pot glycosidation technique of 1,2-linked oligogalactan exploiting chain polymerization of galactose-based cyclic sulfite as a monomer initiated with ceramide-based alcoholic aglycon. Through the concentration dependence of PolyGalCer solutions in water or in MeOH on the turbidity, it is found that PolyGalCer forms associates in both media. From the intersection points, the critical aggregation concentration (CAC) values of PolyGalCer in water and MeOH were estimated. To know the self-assembly and the thermal transition behaviors, we performed dynamic light scattering (DLS) analysis of the associates comprising PolyGalCer in water. The transmission electron microscopy observations of the aqueous sample solution indicate that the solution of PolyGalCer includes large spherical associates. The results clarify that the 1,2-galactan moiety of PolyGalCer skeleton contributes on the kinetic inhibition of large associate formation and the metamorphosis of associates. [Display omitted] [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) can establish infection via two distinct modes: virus-to-cell infection and cell-to-cell transmission. These infections prompt the activation of two types of adaptive immune responses: the cytotoxic T lymphocyte response and the antibody response. In this paper, we study HCV dynamics by developing a multiscale model that incorporates both modes of infection as well as the two types of immune responses. We derive both the basic reproduction number of virus and four immune reproduction numbers for the model. We identify five equilibria, the existence of which depends on the values of basic reproduction number of virus and the immune reproduction numbers. We also establish the global asymptotic stability of the equilibria by employing Lyapunov functions, which further underscores the profound impact of the aforementioned reproduction numbers on the model's overall stability. [ABSTRACT FROM AUTHOR]

A mathematical model for the quantitative analysis of the interaction between cancer cells and cell-mediated immune system with two discrete-time delays, considering the role of antibodies, is studied in this paper. The model is analyzed both analytically and numerically to understand the dynamics of interaction delay and proliferation enhancement effect delay in the eradication of cancer. Hopf bifurcation occurs when one-time delay crosses the critical value in the absence of the other. It is also observed that as we increase any of the delays, it will increase the cancer burden. The analysis shows that a cancer-free state cannot be obtained solely by the killing rate of cytotoxic T-lymphocytes, but humoral response in combination with cell-mediated immune responses plays an important role to eradicate cancer. [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]

Tumor-associated macrophages (TAMs), the main components of infiltrating leukocytes in tumors, often play a key role in promoting cancer development and progression. The tumor-specific microenvironment forces the phenotype of tumor-infiltrating to evolve in a direction favorable to tumor development, that is, the generation of M2-like TAMs. Consequently, the dual intervention of cancer cells and tumor microenvironment has become a research hotspot in the field of tumor immunotherapy. In this contribution, we developed pH-sensitive mesoporous calcium silicate nanocomposites (MCNs) encapsulated with indocyanine green (ICG) to enable the effective combination of photothermal therapy (PTT) and photodynamic therapy (PDT) triggered by the 808 nm near-infrared (NIR) light. The mannose and hyaluronic acid-grafted MCNs specifically targeted TAMs and tumor cells and promoted cell apoptosis both in vitro and in vivo. This paper revealed that irradiation of ICG loaded MCNs with NIR can produce a potent hyperthermia and induce abundant intracellular singlet oxygen generation in the target cells. These results suggest that the novel nanoplatform is believed to facilitate the delivery of chemotherapeutic agents to the tumor microenvironment (TME) to enhance the effects of tumor treatment. [Display omitted] [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]

In this paper, a deterministic model characterizing the within-host infection of Hepatitis C virus (HCV) in intrahepatic and extrahepatic tissues is presented. In addition, the model also includes the effect of the cytotoxic T lymphocyte (CTL) immunity described by a linear activation rate by infected cells. Firstly, the non-negativity and boundedness of solutions of the model are established. Secondly, the basic reproduction number R 01 and immune reproduction number R 02 are calculated, respectively. Three equilibria, namely, infection-free, CTL immune response-free and infected equilibrium with CTL immune response are discussed in terms of these two thresholds. Thirdly, the stability of these three equilibria is investigated theoretically as well as numerically. The results show that when R 01 < 1 , the virus will be cleared out eventually and the CTL immune response will also disappear; when R 02 < 1 < R 01 , the virus persists within the host, but the CTL immune response disappears eventually; when R 02 > 1 , both of the virus and the CTL immune response persist within the host. Finally, a brief discussion will be given. [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]