Dendritic cells (DCs), the strongest antigen-presenting cells, are a focus for orchestrating the immune system in the fight against cancer. Basic scientific investigations elucidating the cellular ...biology of the DCs have resulted in new strategies in this fight, including cancer vaccinology, combination therapy, and adoptive cellular therapy. Although immunotherapy is currently becoming an unprecedented bench-to-bedside success, the overall response rate to the current immunotherapy in patients with gastrointestinal (GI) cancers is pretty low. Here, we have carried out a literature search of the studies of DCs in the treatment of GI cancer patients. We provide the advances in DC-based immunotherapy and highlight the clinical trials that indicate the therapeutic efficacies and toxicities related with each vaccine. Moreover, we also offer the yet-to-be-addressed questions about DC-based immunotherapy. This study focuses predominantly on the data derived from human studies to help understand the involvement of DCs in patients with GI cancers.
T cells are the main effector cells in immune response against tumors. The activation of T cells is regulated by the innate immune system through positive and negative costimulatory molecules. ...Targeting immune checkpoint regulators such as programmed cell death 1 (PD-1)/PD-1 ligand 1 (PD-L1) and CTL antigen 4 (CTLA-4) has achieved notable benefit in a variety of cancers, which leads to multiple clinical trials with antibodies targeting the other related B7/CD28 family members. Recently, five new B7 family ligands, B7-H3, B7-H4, B7-H5, B7-H6, and B7-H7, were identified. Here we review recent understanding of new B7 family checkpoint molecules as they have come to the front of cancer research with the concept that tumor cells exploit them to escape immune surveillance. The aim of this article is to address the structure and expression of the new B7 family molecules as well as their roles in controlling and suppressing immune responses of T cells as well as NK cells. We also discuss clinical significance and contribution of these checkpoint expressions in human cancers.
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Immune system can recognize self vs transformed self. That is why cancer immunotherapy achieves notable benefits in a wide variety of cancers. Recently, several papers reported that immune checkpoint ...blockade therapy led to upregulation of IFNγ and in turn clearance of tumor cells. In this review, we conducted an extensive literature search of recent 5‐year studies about the roles of IFNγ signaling in both tumor immune surveillance and immune evasion. In addition to well‐known functions, IFNγ signaling also induces tumor ischemia and homeostasis program, resulting in tumor clearance and tumor escape, respectively. The yin and the yang of IFNγ signaling are summarized. Thus, this review helps us to comprehensively understand the roles of IFNγ in tumor immunity, which contributes to better design and management of clinical immunotherapy approaches.
IFN‐gamma signaling induces tumor ischemia and homeostasis program, resulting in tumor clearance and tumor escape, respectively. The yin and the yang of IFN‐gamma signaling are summarized in this review.
In situations involving continuous exposure to antigens, such as chronic infections or cancer, antigen‐specific CD8+ T cells can become dysfunctional or exhausted. This change is marked by increased ...expression levels of inhibitory receptors (PD‐1 and Tim‐3). Stem‐like progenitor exhausted (Tpex) cells, a subset of exhausted cells that express TCF‐1 and are mainly found in the lymph nodes, demonstrate the ability to self‐renew and exhibit a high rate of proliferation. Tpex cells can further differentiate into transitional intermediate exhausted (Tex‐int) cells and terminally exhausted (Tex‐term) cells. Alternatively, they can directly differentiate into Tex‐term cells. Tpex cells are the predominant subset that respond to immune checkpoint inhibitors (ICI), making them a prime candidate for improving the efficacy of ICI therapy. This review article aimed to present the latest developments in the field of Tpex formation, expansion, and differentiation in the context of cancer, as well as their responses to ICIs in cancer immunotherapy. Consequently, it may be possible to develop novel treatments that exclusively target Tpex cells, thus improving overall treatment outcomes.
Key points
Tpex cells are located in lymph nodes and TLS.
Several pathways control the differentiation trajectories of Tpex cells, including epigenetic factors, transcription factors, cytokines, age, sex, etc.
(1) Several pathways involving epigenetic factors, such as cBAF, control the differentiation trajectories of Tpex cells. (2) Bio‐behaviour of cancer stem‐like progenitor T cells is regulated by transcription factors such as IKAROS. (3) The cancer stem‐like progenitor T‐cell bio‐behaviour is regulated by cytokines such as IL‐2. (4) Other factors, such as MAP4K1, regulate the cancer stem‐like progenitor T‐cell bio‐behaviour
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Cancer is a leading cause of death worldwide, accounting for millions of deaths every year. Immunotherapy is a groundbreaking approach for treating cancer through harnessing the power of the immune ...system to target and eliminate cancer cells. Cancer vaccines, one immunotherapy approach, have shown promise in preclinical settings, but researchers have struggled to reproduce these results in clinical settings. However, with the maturity of mRNA technology and its success in tackling the recent coronavirus disease 2019 (COVID-19) pandemic, cancer vaccines are expected to regain attention. In this review, we focused on the recent progress made in mRNA-based cancer vaccines over the past five years. The mechanism of action of mRNA vaccines, advancements in neoantigen discovery, adjuvant identification, and delivery materials are summarized and reviewed. In addition, we also provide a detailed overview of current clinical trials involving mRNA cancer vaccines. Lastly, we offer an insight into future considerations for the application of mRNA vaccines in cancer immunotherapy. This review will help researchers to understand the advances in mRNA-based cancer vaccines and explore new dimensions for potential immunotherapy approaches.
Newly emerging super‐resolution imaging techniques provide opportunities for precise observations on cellular microstructures. However, they also impose severe demands on fluorophores. Here, we ...develop a new series of NIR xanthene dyes, named as KRhs, by replacing the 10‐position O of rhodamines with a cyclo‐ketal. KRhs display an intense NIR emission peak at 700 nm with fluorescence quantum yields up to 0.64. More importantly, they, without the aid of enhancing buffer, exhibit stochastic fluorescence off–on switches to support time‐resolved localization of single fluorophore. KRhs are functionalized into KRh‐MitoFix, KRh‐Mem and KRh‐Halo that demonstrate mitochondria, plasma membrane and fusion protein targeting ability, respectively. Consequently, these KRh probes demonstrate straightforward usage for super‐resolution imaging of these targets in live cells. Therefore, KRhs merit future development for fluorescence labeling and super‐resolution imaging in the NIR region.
In this study, the emission of xanthene dye is pushed to the NIR region by replacing the 10‐position O of rhodamines with a cyclo‐ketal. The newly developed KRhs display intense fluorescence peaks at 700 nm (ΦF 0.64) and, more importantly, exhibit stochastic fluorescence off–on switches to support super‐resolution imaging. These KRh derivatives display great potential for fluorescence labeling and super‐resolution imaging in the NIR region.
Lab‐on‐a‐nanoparticle: The triple‐channel optical properties of Mn‐doped ZnS quantum dots (fluorescence, phosphorescence, and light scattering) are explored to develop a multidimensional sensing ...device for the discrimination of proteins in a lab‐on‐a‐nanoparticle approach (see picture).
Eomes, a T-box transcription factor, is known important for both function and homeostasis of effector and memory T cells, but was recently also implicated in CD8
T cell exhaustion. However, whether ...and how Eomes might regulate effector functions or exhaustion of CD8
T cells, especially in the tumor setting, is unknown. Here we first show, as tumor progressed, Eomes expression was elevated in tumor-infiltrating CD8
T cells, especially in PD-1
Tim-3
exhausted CD8
T cells. Complete loss of Eomes in T cells resulted in impaired development of anti-tumor CTLs, whereas deletion of one allele of
in T cells decreased development of exhausted CD8
T cells, which offered better tumor control. Integrative analysis of RNAseq and ChIPseq of Eomes-overexpressing T cells revealed that high levels of Eomes expression directly controlled expression of T cell exhaustion genes, such as
. In addition, Eomes might compete with T-bet binding to regulatory genomic loci to antagonize T-bet functions. Collectively, Eomes exerts bimodal functions in CD8
T cells in tumor.
The World Health Organization has declared SARS-CoV-2 virus outbreak a worldwide pandemic. However, there is very limited understanding on the immune responses, especially adaptive immune responses ...to SARS-CoV-2 infection. Here, we collected blood from COVID-19 patients who have recently become virus-free, and therefore were discharged, and detected SARS-CoV-2-specific humoral and cellular immunity in eight newly discharged patients. Follow-up analysis on another cohort of six patients 2 weeks post discharge also revealed high titers of immunoglobulin G (IgG) antibodies. In all 14 patients tested, 13 displayed serum-neutralizing activities in a pseudotype entry assay. Notably, there was a strong correlation between neutralization antibody titers and the numbers of virus-specific T cells. Our work provides a basis for further analysis of protective immunity to SARS-CoV-2, and understanding the pathogenesis of COVID-19, especially in the severe cases. It also has implications in developing an effective vaccine to SARS-CoV-2 infection.
•SARS-CoV-2-specific antibodies are detected in COVID-19 convalescent subjects•Most COVID-19 convalescent individuals have detectable neutralizing antibodies•Cellular immune responses to SARS-CoV-2 are found in COVID-19 convalescent subjects•Neutralization antibody titers correlate with the numbers of virus-specific T cells.
In blood samples from COVID-19 convalescent subjects, Ni et al. have detected SARS-CoV-2-specific humoral and cellular immunity. Most subjects display serum neutralizing activities, which correlate with the numbers of virus-specific T cells.
Chronic obstructive pulmonary disease (COPD) is currently the third largest cause of human mortality in the world after stroke and heart disease. COPD is characterized by sustained inflammation of ...the airways, leading to destruction of lung tissue and declining pulmonary function. The main risk factor is known to be cigarette smoke currently. However, the strategies for prevention and treatment have not altered significantly for many years. A growing body of evidences indicates that the immune system plays a pivotal role in the pathogenesis of COPD. The repeated and progressive activation of immune cells is at least in part the source of this chronic inflammation. In this review paper, we have conducted an extensive literature search of the studies of immune cells in COPD patients. The objective is to assess the contributions of different immune cell types, the imbalance of pro/anti-inflammatory immune cells, such as M1/M2 macrophages, Tc1/Tc10, and Th17/Treg, and their mediators in the peripheral blood as well as in the lung to the pathogenesis of COPD. Therefore, understanding their roles in COPD development will help us find the potential target to modify this disease. This review focuses predominantly on data derived from human studies but will refer to animal studies where they help understand the disease in humans.
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