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The article highlights the top papers on reproduction research in 2004-2008. According to the author, the top two papers include J. Hanna's paper on the role of decidual NK cells in regulating key developmental processes at the human fetal-maternal inteface and M. Xu's paper on tissue-engineered follicles, which produce live, fertile offspring. Other papers that have seen important advances include the immunology of reproduction and the effect of environmental toxins on reproduction.

Gastric cancer is the fifth leading cause of cancer-related deaths worldwide. As the diagnosis of early gastric cancer is difficult, most patients are at a late stage of cancer progression when diagnosed. The current therapeutic approaches based on surgical or endoscopic resection and chemotherapy indeed improve patients' outcomes. Immunotherapy based on immune checkpoint inhibitors has opened a new era for cancer treatment, and the immune system of the host is reshaped to combat tumor cells and the strategy differs according to the patient's immune system. Thus, an in-depth understanding of the roles of various immune cells in the progression of gastric cancer is beneficial to application for immunotherapy and the discovery of new therapeutic targets. This review describes the functions of different immune cells in gastric cancer development, mainly focusing on T cells, B cells, macrophages, natural killer cells, dendritic cells, neutrophils as well as chemokines or cytokines secreted by tumor cells. And this review also discusses the latest advances in immune-related therapeutic approaches such as immune checkpoint inhibitors, CAR-T or vaccine, to reveal potential and promising strategies for gastric cancer treatment. [ABSTRACT FROM AUTHOR]

Immunogenic features of some malignancies have aroused interest in immunotherapy of cancer. Immunotherapy seems most effective in patients with a small tumour burden, and the focus of immunotherapy trials has, thus, lately been on adjuvant treatment. To enable further development of immunotherapy we need to know more about the mechanisms involved in host defence, especially when the system is influenced by extrinsic factors, that is, immunomodulative agents. T lymphocytes play an important role in the host defence against tumour cells trying to escape from immune surveillance. The mechanisms that regulate the host defence systems are complex, and the influence of extrinsic factors such as immunotherapeutic agents is poorly understood. Most data on lymphocyte subsets in malignant disease originate from melanoma or renal cell carcinoma (RCC) studies, although there are scattered data on lymphocyte subsets also in other malignancies. There are several studies implying that the relative amount of CD4+, CD8+, and natural killer (NK) cells may be important and that, by reducing the tumour burden or by using different therapeutic agents, we can stimulate the host defence. However, only some of these studies imply that these changes can have an impact on clinical outcome and prognosis. The findings of the studies reviewed in this paper are mostly encouraging, but whether the lymphocyte subsets have any value as prognostic markers in patients with malignancies receiving immunotherapy is still unclear. Large randomized immunotherapy trials including an observation arm give an ideal opportunity to recognize those immunological changes that are due to therapy, related to the natural host defence, or whether they have any prognostic value. [ABSTRACT FROM AUTHOR]

Ligands for natural killer (NK) cell activating receptors can be released from tumor cells and are believed to promote tumor growth by acting as decoys for effector lymphocytes. In a recent paper published in Science, Deng et al. report another scenario in which a shed form of the MULT1 mouse NKG2D ligand boosts NK cell functions. [ABSTRACT FROM AUTHOR]

Presents an update on papers related to immunology as of January 2003. Role of a peptide in the activation of natural killer cells; Discovery of the non-T-cell activation linker; Adaptor involved in Toll-like receptor signaling.

Examines the characterization of rhesus monkey CD94/NKG2 family members and the identification of novel transmembrane-deleted forms of NKG2-A, B, C, and D. Expression of the members of the cell surface receptor CD94/NKG2 family of molecules by natural killer cells; Amplification of circular DNA with primers specific for the 5' and 3' untranslated regions of human CD94; Composition of a 32-amino acid deletion that spans the transmembrane domain of mmNKG2-A in the predicted amino acid sequence.

Introduction: Endometriosis is a risk factor for low-grade serous, clear cell, and endometroid ovarian carcinoma. In both endometriosis and ovarian carcinoma, immunological factors are associated with clinical outcome. Chronic inflammation in endometriosis may be linked to tumorigenesis, but exact processes contributing to endometriosis-associated ovarian carcinoma remain unknown. This review aims to describe potential immunological factors involved in the malignant transformation of endometriosis into ovarian carcinoma. Methods: PubMed and Embase were searched from inception up to October 2020 for studies comparing immunological processes in endometriosis and endometriosis-associated ovarian carcinoma. Results: Detailed analysis of immune components in the malignant transformation of endometriosis into endometriosis-associated ovarian carcinoma is lacking. Altered levels of chemokines and cytokines as IL-6, IL-8, IL-10, and TNF-α are reported and the function, number and polarization of NK cells, dendritic cells, and monocytes differ between endometriosis and associated ovarian carcinoma compared to healthy tissue. In addition, altered inflammasome and complement systems, indicate a role for the immune system in the carcinogenesis of endometriosis. Conclusion: Chronic inflammation in endometriosis may potentially drive inflammation-induced carcinogenesis in endometriosis-associated ovarian carcinoma. Exact immunological pathways and cellular processes remain unknown and require more thorough investigation. [ABSTRACT FROM AUTHOR]

Valproic acid (VPA) is a drug commonly used for epileptic seizure control. Recently, it has been shown that VPA alters the activation of several immune cells, including Natural Killer (NK) cells, which play an important role in the containment of viruses and intracellular bacteria. Although VPA can increase susceptibility to extracellular pathogens, it is unknown whether the suppressor effect of VPA could affect the course of intracellular bacterial infection. This study aimed to evaluate the role of VPA during Listeria monocytogenes (L.m) infection, and whether NK cell activation was affected. We found that VPA significantly augmented mortality in L.m infected mice. This effect was associated with increased bacterial load in the spleen, liver, and blood. Concurrently, decreased levels of IFN-γ in serum and lower splenic indexes were observed. Moreover, in vitro analysis showed that VPA treatment decreased the frequency of IFN-γ-producing NK cells within L.m infected splenocytes. Similarly, VPA inhibited the production of IFN-γ by NK cells stimulated with IL-12 and IL-18, which is a crucial system for early IFN-γ production in listeriosis. Finally, VPA decreased the phosphorylation of STAT4, p65, and p38, without affecting the expression of IL-12 and IL-18 receptors. Altogether, our results indicate that VPA increases the susceptibility to Listeria monocytogenes infection and suggest that NK cell is one of the main targets of VPA, but further work is needed to ascertain this effect. [ABSTRACT FROM AUTHOR]

In this study, we sought to fill an important gap in fundamental immunology research by conducting a comprehensive systems immunology analysis of daily variation in the normal human peripheral immune system. Although variation due to circadian rhythmicity was not a significant source of variation in daily B-cell levels or any CD4+ functional subset, it accounted for more than 25% of CD4+ regulatory T-cell variation and over 50% of CD8+ central memory variation. Circadian rhythmicity demonstrated phase alignment within functional phenotypes. In addition, we observed that previously-described mechanistic relationships can also appear in the peripheral system as phase shifting in rhythmic patterns. We identified a set of immune factors which are ubiquitously correlated with other factors and further analysis also identified a tightly-correlated "core" set whose relational structure persisted after analytically removing circadian-related variation. This core set consisted of CD8+ and its subpopulations and the NK population. In sum, the peripheral immune system can be conceptualized as a dynamic, interconnected wave-field repeating its pattern on a daily basis. Our data provide a comprehensive inventory of synchronization and correlation within this wave-field and we encourage use of our data to discover unknown mechanistic relationships which can then be tested in the laboratory. [ABSTRACT FROM AUTHOR]

The article presents abstracts of papers on immunology including "Ozone exposure in a mouse model induces airway hyperactivity that requires the presence of natural killer T cells and IL-17," by M. Pichavant and colleagues, and "Repression of the transcription factor Th-POX by Runx complexes in cytotoxic T cell development," by R. Setoguchi and colleagues.

Discusses research by Cornelia Urlich and colleagues published in the "Journal of the American Dietetic Association" on the impact of yo-yo dieting on the immune function. Examination of interview responses from women who underwent weight loss diets; Implications of weight cycling for natural killer cell function; Recommended solutions to the negative effects of weight loss on the immune system.

The article presents brief on Immunology research. A research on the role of mitochondria in lymphocyte chemotaxis is presented. An overview on the iteractions between NK cells and accessory cells to determine immune response to P. falciparum is presented. The physiological functions of CD28 in t-cells is discussed.

Natural killer (NK) cell activation is strictly regulated to ensure that healthy cells are preserved, but tumour-transformed or virus-infected cells are recognized and eliminated. To carry out this selective killing, NK cells have an ample repertoire of receptors on their surface. Signalling by inhibitory and activating receptors by interaction with their ligands will determine whether the NK cell becomes activated and kills the target cell. Here, we show reduced expression of NKp46, NKp30, DNAM-1, CD244 and CD94/NKG2C activating receptors on NK cells from acute myeloid leukaemia patients. This reduction may be induced by chronic exposure to their ligands on leukaemic blasts. The analysis of ligands for NK cell-activating receptors showed that leukaemic blasts from the majority of patients express ligands for NK cell-activating receptors. DNAM-1 ligands are frequently expressed on blasts, whereas the expression of the NKG2D ligand MICA/B is found in half of the patients and CD48, a ligand for CD244, in only one-fourth of the patients. The decreased expression of NK cell-activating receptors and/or the heterogeneous expression of ligands for major receptors on leukaemic blasts can lead to an inadequate tumour immunosurveillance by NK cells. A better knowledge of the activating receptor repertoire on NK cells and their putative ligands on blasts together with the possibility to modulate their expression will open new possibilities for the use of NK cells in immunotherapy against leukaemia. [ABSTRACT FROM AUTHOR]

Neutrophils are the main effector cells during inflammation, but they can also control excessive inflammatory responses by secreting anti-inflammatory cytokines. However, the mechanisms that modulate their plasticity remain unclear. We now show that systemic serum amyloid A 1 (SAA-1) controls the plasticity of neutrophil differentiation. SAA-1 not only induced anti-inflammatory interleukin 10 (IL-10)-secreting neutrophils but also promoted the interaction of invariant natural killer T cells (iNKT cells) with those neutrophils, a process that limited their suppressive activity by diminishing the production of IL-10 and enhancing the production of IL-12. Because SAA-1-producing melanomas promoted differentiation of IL-10-secreting neutrophils, harnessing iNKT cells could be useful therapeutically by decreasing the frequency of immunosuppressive neutrophils and restoring tumor-specific immune responses. [ABSTRACT FROM AUTHOR]

Lymph nodes (LNs) capture microorganisms that breach the body’s external barriers and enter draining lymphatics, limiting the systemic spread of pathogens. Recent work has shown that CD11b+CD169+ macrophages, which populate the subcapsular sinus (SCS) of LNs, are critical for the clearance of viruses from the lymph and for initiating antiviral humoral immune responses. Here we show, using vesicular stomatitis virus (VSV), a relative of rabies virus transmitted by insect bites, that SCS macrophages perform a third vital function: they prevent lymph-borne neurotropic viruses from infecting the central nervous system (CNS). On local depletion of LN macrophages, about 60% of mice developed ascending paralysis and died 7–10 days after subcutaneous infection with a small dose of VSV, whereas macrophage-sufficient animals remained asymptomatic and cleared the virus. VSV gained access to the nervous system through peripheral nerves in macrophage-depleted LNs. In contrast, within macrophage-sufficient LNs VSV replicated preferentially in SCS macrophages but not in adjacent nerves. Removal of SCS macrophages did not compromise adaptive immune responses against VSV, but decreased type I interferon (IFN-I) production within infected LNs. VSV-infected macrophages recruited IFN-I-producing plasmacytoid dendritic cells to the SCS and in addition were a major source of IFN-I themselves. Experiments in bone marrow chimaeric mice revealed that IFN-I must act on both haematopoietic and stromal compartments, including the intranodal nerves, to prevent lethal infection with VSV. These results identify SCS macrophages as crucial gatekeepers to the CNS that prevent fatal viral invasion of the nervous system on peripheral infection. [ABSTRACT FROM AUTHOR]

In addition to the direct targeting effects on HER2-positive cells, trastuzumab may have a therapeutic role modulating the activity of the cellular immune system in patients with breast cancer. To investigate this further, the balance of T-regulatory (T(reg)), Th17, natural killer (NK) and NK T (NKT) cells before, during and after trastuzumab therapy was investigated. Sequential frequencies of circulating T(reg) cells, Th17 cells, NK and NKT cells were measured in peripheral blood of breast cancer patients and normal controls throughout therapy. Individuals with breast cancer had significantly higher T(reg) frequencies of peripheral blood compared with healthy controls (9.2 or 8.6 vs 6%; P<0.05), and no significant differences in T(reg) frequencies were observed between HER2-positive and HER2-negative individuals. The number of Th17 cells was lowest in HER2-positive patients compared with both healthy controls and HER2-negative patients (0.31 vs 0.75% or 0.84%; P=0.01). There appeared to be an inverse relationship between T(reg) and Th17 frequencies in metastatic breast cancer (MBC) with T(reg) levels significantly reduced during treatment with trastuzumab (P=0.04), whereas Th17 frequencies were concomitantly increased (P=0.04). This study supports earlier data that T(reg) cells are present at higher frequencies in breast cancer patients compared with healthy individuals. For the first time, we show that HER2-positive individuals with breast carcinomas have reduced numbers of circulating Th17 cells, which appear, in turn to have an inverse relationship with T(reg) frequency in MBC. The change in balance of the T(reg) : Th17 ratio appears to characterise the cancer state, and furthermore, is disrupted by trastuzumab therapy. [ABSTRACT FROM AUTHOR]

The conventional wisdom is that cell-surface receptors interact with ligands expressed on other cells to mediate cell-to-cell communication (trans interactions). Unexpectedly, it has recently been found that two classes of receptors specific for MHC class I molecules not only interact with MHC class I molecules expressed on opposing cells, but also with those on the same cell. These cis interactions are a feature of immunoreceptors that inhibit, rather than activate, cellular functions. Here, we review situations in which cis interactions have been observed, the characteristics of receptors that bind in trans and cis, and the biological roles of cis recognition. [ABSTRACT FROM AUTHOR]

Presents updates on immunology research as of February 2002. Non-participation of interleukin-9 in either the development of allergen-induced pulmonary inflammation nor airway hyper-reactivity; Homeostatic competition between T cells revealed by conditional inactivation of the mouse Cd4 gene; Identification of the earliest prethymic bipotent T/NK progenitor in murine fetal liver.

Isogenic mouse strains have previously been characterized as susceptible or resistant to Paracoccidioides brasiliensis infection; the former presented anergy in delayed-type hypersensitivity reactions (DTH) and progressive disease with high numbers of colony-forming units (CFU), while the later presented preserved DTH responses and control of the infectious process. Here, we studied whether susceptible mice infected with P. brasiliensis and treated with the antifungal drug trimethoprim-sulfamethoxazole (SXT) had their behavior pattern altered to the one observed in infected resistant mice. Therapy with either 30 or 150 mg SXT day-1 kg-1, instituted 24 h after infection, elicited more adequate DTH responses than those of non-treated mice, and also diminished the number of viable fungi in the spleen and lungs, but not in epiploo and liver, indicating a partial control of the infectious process. This phenomenon was confirmed by histopathological analyses, in which the spleen was found to be the organ in which differences between the treated and non-treated groups were most remarkable. In control non-treated mice, the spleen parenchyma showed multiple granulomatous foci presenting giant cells, plasmocytes and many yeasts of P. brasiliensis with well-preserved morphology and abundant budding, whereas SXT-treated mice, independently of the dosage used, had no granulomas within the parenchyma and only few capsular lesions, mainly composed of pseudoxantomatous macrophages. Treatment with 150 mg day-1 kg-1 (the dose considered to evoke best responses in CFU assays when therapy was instituted 24 h after infection), initiated at different times after infection, did not led to sustained DTH reactions, but provided an effective control of the disease when therapy began until the 15th day post infection, as showed by CFU assays. We conclude that reversal from the susceptible to the resistant pattern in experimental paracoccidioidomycosis can occur, but only when therapy with an adequate SXT dosage is instituted at a very initial phase of the infection. These protocols may constitute a model for further investigations concerning responses during antifungal therapy. [ABSTRACT FROM AUTHOR]

HLA class I expression is altered in a significant fraction of the tumor types reviewed here, reflecting either immune pressure or, simply, the accumulation of pathological changes and alterations. However, in all tumor types analyzed, a majority of the tumors express HLA class I, with a general tendency for the more severe alterations to be found in later-stage and less differentiated tumors. These results are encouraging for the development of specific immunotherapies, especially considering that (1) the relatively low sensitivity of immunohistochemical techniques might underestimate HLA expression in tumors, (2) class I expression can be induced in tumor cells as a result of local inflammation and lymphokine release, and (3) class I-negative cells would be predicted to be sensitive to lysis by natural killer cells. [ABSTRACT FROM AUTHOR]

The article reports on the study which reveals that the increasing numbers of natural killer (NK) cell yields an essential role in keeping the harmony during viral infection. It notes that during viral infection, NK cells help in preventing T cell-mediated immunopathology. It also discusses the role of Ly49H, a NK cell activating receptor, in the prevention of immunopathology caused by the adaptive immune system.

The article discusses the role of Cytotoxic CD8+ T cells in controlling the spread of intracellular pathogens through the lysis of infected cells and the cytokine-dependent activation of intracellular microbicides. It presents the recent studies which have identified two T-box factors ― T-bet and eosmesodermin (EOSMES) ― that regulate the cytolytic effector mechanism of CD8+ T cells. It also analyzes the function of T-bet and EOMES in effector T cells.

An introduction is presented in which the editor discusses various reports within the issue on topics including immunology, natural killer cells, and angiogenesis.

The article focuses on two separate studies which had visualized invariant natural killer T (iNKT) cells being activated in vivo. Both of these studies suggested a significant role for specialized tissue-resident macrophage populations in iNKT cell activation. One study tracked the behaviour of fluorescently labelled iNKT cells in lymph node. However, the second study visualized the behaviour of iNKT cells in the liver.

The article provides an overview of the topics related to immunology, that are discussed in this issue. An article proposed that invariant natural killer T cells may have a crucial role in regulating the development of asthma. Another article focuses on targeting lung dendritic cells as another effective strategy against asthma. One article presented information on recent experiments with the development of an effective AIDS vaccine.

Comments on several published studies on immunology. Importance of natural killer T cells; Significance of intercellular pores on the immune system; Results of the insertional mutagenesis that occurred during a clinical trial for the treatment of X-linked severe combined immunodeficiency.