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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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

Tim-3 is a transmembrane protein that is highly expressed on subsets of chronically stimulated CD4+ helper and CD8+ cytotoxic T cells, with more transient expression during acute activation and infection. Tim-3 is also constitutively expressed by multiple types of myeloid cells. Like other TIM family members, Tim-3 can bind to phosphatidylserine displayed by apoptotic cells, and this interaction has been shown to mediate uptake of such cells by dendritic cells and cross-presentation of antigens to CD8+ T cells. In contrast, how the recognition of PS by Tim-3 might regulate the function of Tim- 3+ T cells is not known. In their recent paper, Lemmon and colleagues demonstrate for the first time that recognition of PS by Tim-3 leads to enhanced T cell activation. [ABSTRACT FROM AUTHOR]

Despite many recent advances on cancer novel therapies, researchers have yet a long way to cure cancer. They have to deal with tough challenges before they can reach success. Nonetheless, it seems that recently developed immunotherapy-based therapy approaches such as adoptive cell transfer (ACT) have emerged as a promising therapeutic strategy against various kinds of tumors even the cancers in the blood (liquid cancers). The hematological (liquid) cancers are hard to be targeted by usual cancer therapies, for they do not form localized solid tumors. Until recently, two types of ACTs have been developed and introduced; tumor-infiltrating lymphocytes (TILs) and chimeric antigen receptor (CAR)-T cells which the latter is the subject of our discussion. It is interesting about engineered CAR-T cells that they are genetically endowed with unique cancer-specific characteristics, so they can use the potency of the host immune system to fight against either solid or liquid cancers. Multiple myeloma (MM) or simply referred to as myeloma is a type of hematological malignancy that affects the plasma cells. The cancerous plasma cells produce immunoglobulins (antibodies) uncontrollably which consequently damage the tissues and organs and break the immune system function. Although the last few years have seen significant progressions in the treatment of MM, still a complete remission remains unconvincing. MM is a medically challenging and stubborn disease with a disappointingly low rate of survival rate. When comparing the three most occurring blood cancers (i.e., lymphoma, leukemia, and myeloma), myeloma has the lowest 5-year survival rate (around 40%). A low survival rate indicates a high mortality rate with difficulty in treatment. Therefore, novel CAR-T cell-based therapies or combination therapies along with CAT-T cells may bring new hope for multiple myeloma patients. CAR-T cell therapy has a high potential to improve the remission success rate in patients with MM. To date, many preclinical and clinical trial studies have been conducted to investigate the ability and capacity of CAR T cells in targeting the antigens on myeloma cells. Despite the problems and obstacles, CAR-T cell experiments in MM patients revealed a robust therapeutic potential. However, several factors might be considered during CAR-T cell therapy for better response and reduced side effects. Also, incorporating the CAT-T cell method into a combinational treatment schedule may be a promising approach. In this paper, with a greater emphasis on CAR-T cell application in the treatment of MM, we will discuss and introduce CAR-T cell's history and functions, their limitations, and the solutions to defeat the limitations and different types of modifications on CAR-T cells. [ABSTRACT FROM AUTHOR]

Despite many recent advances on cancer novel therapies, researchers have yet a long way to cure cancer. They have to deal with tough challenges before they can reach success. Nonetheless, it seems that recently developed immunotherapy-based therapy approaches such as adoptive cell transfer (ACT) have emerged as a promising therapeutic strategy against various kinds of tumors even the cancers in the blood (liquid cancers). The hematological (liquid) cancers are hard to be targeted by usual cancer therapies, for they do not form localized solid tumors. Until recently, two types of ACTs have been developed and introduced; tumor-infiltrating lymphocytes (TILs) and chimeric antigen receptor (CAR)-T cells which the latter is the subject of our discussion. It is interesting about engineered CAR-T cells that they are genetically endowed with unique cancer-specific characteristics, so they can use the potency of the host immune system to fight against either solid or liquid cancers. Multiple myeloma (MM) or simply referred to as myeloma is a type of hematological malignancy that affects the plasma cells. The cancerous plasma cells produce immunoglobulins (antibodies) uncontrollably which consequently damage the tissues and organs and break the immune system function. Although the last few years have seen significant progressions in the treatment of MM, still a complete remission remains unconvincing. MM is a medically challenging and stubborn disease with a disappointingly low rate of survival rate. When comparing the three most occurring blood cancers (i.e., lymphoma, leukemia, and myeloma), myeloma has the lowest 5-year survival rate (around 40%). A low survival rate indicates a high mortality rate with difficulty in treatment. Therefore, novel CAR-T cell-based therapies or combination therapies along with CAT-T cells may bring new hope for multiple myeloma patients. CAR-T cell therapy has a high potential to improve the remission success rate in patients with MM. To date, many preclinical and clinical trial studies have been conducted to investigate the ability and capacity of CAR T cells in targeting the antigens on myeloma cells. Despite the problems and obstacles, CAR-T cell experiments in MM patients revealed a robust therapeutic potential. However, several factors might be considered during CAR-T cell therapy for better response and reduced side effects. Also, incorporating the CAT-T cell method into a combinational treatment schedule may be a promising approach. In this paper, with a greater emphasis on CAR-T cell application in the treatment of MM, we will discuss and introduce CAR-T cell's history and functions, their limitations, and the solutions to defeat the limitations and different types of modifications on CAR-T cells. [ABSTRACT FROM AUTHOR]

Human immunodeficiency virus (HIV) and human T-lymphotropic virus type I (HTLV-I) are two retroviruses that infect the susceptible CD 4 + T cells. It is known that HIV and HTLV-I have in common a way of transmission through direct contact with certain body fluids related to infected individuals. Therefore, it is not surprising that a mono-infected person with one of these viruses can be co-infected with the other virus. In the literature, a great number of mathematical models has been presented to describe the within-host dynamics of HIV or HTLV-I mono-infection. However, the within-host dynamics of HIV/HTLV-I co-infection has not been modeled. In this paper, we develop a new within-host HIV/HTLV-I co-infection model. The model includes the impact of Cytotoxic T lymphocytes (CTLs) immune response, which is important to control the progression of viral co-infection. The model describes the interaction between susceptible CD 4 + T cells, silent HIV-infected cells, active HIV-infected cells, silent HTLV-infected cells, Tax-expressing HTLV-infected cells, free HIV particles, HIV-specific CTLs and HTLV-specific CTLs. We first show the nonnegativity and boundedness of the model's solutions and then we calculate all possible equilibria. We derive the threshold parameters which govern the existence and stability of all equilibria of the model. We prove the global asymptotic stability of all equilibria by utilizing Lyapunov function and LaSalle's invariance principle. We have presented numerical simulations to illustrate the effectiveness of our main results. In addition, we discuss the effect of HTLV-I infection on the HIV-infected patients and vice versa. [ABSTRACT FROM AUTHOR]

Discrete tissue niches are emerging as essential prerequisites enabling cell communication and function in both homeostasis and disease. In a recent Cell paper, Di Pilato et al. identify a unique dendritic cell-cytotoxic T cell crosstalk within the perivascular space that facilitates T cell survival and proliferation and drives anti-tumor activity. [ABSTRACT FROM AUTHOR]

Malaria is a life-threatening disease caused by infection with Plasmodium parasites. The goal of developing an effective malaria vaccine is yet to be reached despite decades of massive research efforts. CD4+ helper T cells, CD8+ cytotoxic T cells, and γδ T cells are associated with immune responses to both liver-stage and blood-stage Plasmodium infection. The immune responses of T cell-lineages to Plasmodium infection are associated with both protection and immunopathology. Studies with mouse model of malaria contribute to our understanding of host immune response. In this paper, we focus primarily on mouse malaria model with blood-stage Plasmodium berghei infection and review our knowledge of T cell immune responses against Plasmodium infection. Moreover, we also discuss findings of experimental human studies. Uncovering the precise mechanisms of T cell-mediated immunity to Plasmodium infection can be accomplished through further investigations using mouse models of malaria with rodent Plasmodium parasites. Those findings would be invaluable to advance the efforts for development of an effective malaria vaccine. [ABSTRACT FROM AUTHOR]

Chronic lymphocytic leukaemia (CLL) is the most common leukaemia among adults. It is the clonal expansion of B cells expressing CD19 and CD5. Despite significant progress in treatment, CLL is still incurable. γδ T cells comprise an important subset of the cytotoxic T cells. Although γδ T cells in CLL are dysfunctional, they still can possibly be used for immunotherapy. The current paper reviews our understanding of γδ T lymphocytes in CLL. [ABSTRACT FROM AUTHOR]

• Major immune effector cells like CD8+ T lymphocytes and natural killer cells are able to kill or inhibit Hepatocellular carcinoma (HCC) cells and their cytotoxic ability can be enhanced or down-regulated by certain cytokines or drugs. • HCC cells can impair the function of major immune effector cells through a variety of mechanisms. • Organoids or direct contact cell co-culture especially with primary HCC cells and tumor infiltrating lymphocytes provide better understanding of cell–cell interactions between major immune effector cells and HCC cells. • Immunotherapy like checkpoint inhibitors and adoptive cell transfer showed notable effectiveness and safety in preventing HCC recurrence as adjuvant therapy. Hepatocellular carcinoma (HCC) is the most common liver neoplasm with high morbidity and mortality. Tumor immunotherapy might be promising adjuvant therapy for HCC after surgery. To better develop HCC immunotherapy, comprehensive understanding of cell–cell interactions between immune effector cells and HCC cells remains crucial. To review the existing studies to summarize the cell–cell interactions between major immune effector cells and HCC cells providing new data for HCC immunotherapy. A systematic review was conducted by searching PubMed database covering all papers published in recent five years up to January 2020. The guidelines of the preferred reporting items for systematic reviews were firmly followed. There are 9 studies researching the interactions between CD8+ T lymphocytes and HCC cells and 22 studies researching that between natural killer (NK) cells and HCC cells. Among the 9 studies, 6 studies reported that CD8+ T lymphocytes showed cytotoxicity towards HCC cells while 3 studies found CD8+ T lymphocytes were impaired by HCC cells. Among the 22 studies, 20 studies presented that NK cells could inhibit HCC cells. Two studies were found to report NK cell dysfunction in HCC. Based on the systematic analysis, we concluded that CD8+ T lymphocytes and NK cells can inhibit HCC cells. While in turn, HCC cells can also result in the dysfunction of those effector cells through various mechanisms. Organoids and direct contact cell co-culture with primary HCC cells and TILs should be the most innovative way to investigate the interactions and develop novel immunotherapy. [ABSTRACT FROM AUTHOR]