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• Anti-CD1d treatment suppress Th2 cell responses in asthma by suppresses immunogenic maturation of LDCs. • Anti-CD1d treatment lowers the abundance and activation of lung iNKT cells in asthma. • The influences of anti-CD1d treatment in LDCs of asthma were dependent on lung iNKT cells. • The influences of anti-CD1d treatment in LDCs of asthma were relevant to the downregulation of CD40L expression on lung iNKT cells. Our previous findings show that invariant natural killer T (iNKT) cells can promote immunogenic maturation of lung dendritic cells (LDCs) to enhance Th2 cell responses in asthma. It has been accepted that recognition of glycolipid antigens presented by CD1d molecules by the T cell receptors of iNKT cells leads to iNKT cell activation. Therefore, we examine the immunoregulatory influences of anti-CD1d treatment on Th2 cell response and immunogenic maturation of LDCs and subsequently explored whether these influences were dependent on lung iNKT cells in asthmatic mice. We discovered that in wild-type mice sensitized and challenged with house dust mite or ovalbumin (OVA), anti-CD1d treatment inhibited Th2 cell response and immunogenic maturation of LDCs. LDCs from asthmatic mice with anti-CD1d treatment had a markedly decreased influence on Th2 cell responses in vivo and in vitro. Furthermore, anti-CD1d treatment reduced the abundance and activation of lung iNKT cells in asthmatic mice. Moreover, in asthmatic iNKT cell-deficient Jα18-/- mice, anti-CD1d treatment did not influence Th2 cell responses and immunogenic maturation of LDCs. Meanwhile, the quantity of CD40L+ iNKT cells in asthmatic mice was significant decreased by anti-CD1d treatment. Finally, the inhibition of anti-CD1d treatment on LDC immunogenic maturation and Th2 cell responses in asthmatic mice was reversed by anti-CD40 treatment. Our data suggest that anti-CD1d treatment can suppress Th2 cell responses through inhibiting immunogenic maturation of LDCs dependent on lung iNKT cells, which could be partially related to the downregulation of CD40L expression on lung iNKT cells in asthmatic mice. [ABSTRACT FROM AUTHOR]

• High expression of IL-17A promotes the growth and metastasis of many tumors, leading to a poor prognosis for cancer patients. • IL-17A promotes resistance to anti-PD-1 therapy by increasing PD-L1 expression in patients with various cancers, and combined anti-IL-17A and anti-PD-1 therapy can significantly improve efficacy. • IL-17A levels in cancer patients may be a predictor of the efficacy of combination therapy. Interleukin 17A (IL-17A) is a major member of the IL-17 cytokine family and is produced mainly by T helper 17 (Th17) cells. Other cells such as CD8+ T cells, γδ T cells, natural killer T cells and innate lymphoid-like cells can also produce IL-17A. In healthy individuals, IL-17A has a host-protective capacity, but excessive elevation of IL-17A is associated with the development of autoimmune diseases and cancer. Monoclonal antibodies (mAbs) targeting IL-17A (e.g., ixekizumab and secukinumab) or IL-17A receptor (IL-17RA) (e.g., brodalumab) would be investigated as potential treatments for these diseases. Currently, the application of IL-17A-targeted drugs in autoimmune diseases will provide new ideas for the treatment of tumors, and its combined application with immune checkpoint inhibitors has become a research hotspot. This article reviews the mechanism of action of IL-17A and the application of anti-IL-17A antibodies, focusing on the research progress on the mechanism of action and therapeutic blockade of IL-17A in various tumors such as colorectal cancer (CRC), lung cancer, gastric cancer and breast cancer. Moreover, we also include the results of therapeutic blockade in the field of cancer as well as recent advances in the regulation of IL-17A signaling. [ABSTRACT FROM AUTHOR]

• We have elucidated a novel mechanism of neutrophil function in promoting APAP hepatotoxicity via the release of pro-inflammatory and cytotoxic IFN-γ. • Neutrophils are the major producer of hepatic IFN-γ in AILI. • Given the functional plasticity of neutrophils in sterile tissue injury, caution should be used when designing innovative strategies to prevent neutrophil-mediated liver damage without compromising their activity in restoring tissue homeostasis. • These findings advance the current understanding of the immunological aspects of APAP-induced hepatic sterile inflammation and tissue injury. Drug (e.g., acetaminophen, APAP)-associated hepatotoxicity is the major cause of acute liver failure. Emerging evidence shows that initial tissue damage caused by APAP triggers molecular and cellular immune responses, which can modulate the severity of hepatoxicity. The pro-inflammatory and cytotoxic cytokine interferon (IFN)-γ has been reported as a key molecule contributing to APAP-induced liver injury (AILI). However, its cellular source remains undetermined. In the current study, we show that elevation of serum IFN-γ in patients with drug hepatotoxicity correlates with disease severity. Neutralization of IFN-γ in a mouse model of AILI effectively reduces hepatotoxicity. Strikingly, we reveal that IFN-γ is expressed primarily by hepatic neutrophils, not by conventional immune cells with known IFN-γ-producing capability, e.g., CD8+ T cells, CD4+ T cells, natural killer cells, or natural killer T cells. Upon encountering APAP-injured hepatocytes, neutrophils secrete cytotoxic IFN-γ further causing cell stress and damage, which can be abrogated in the presence of blocking antibodies for IFN-γ or IFN-γ receptor. Furthermore, removal of neutrophils in vivo substantially decreases hepatic IFN-γ levels concomitantly with reduced APAP hepatotoxicity, whereas adoptive transfer of IFN-γ-producing neutrophils confers IFN-γ-/- mice susceptibility to APAP administration. Our findings uncover a novel mechanism of neutrophil action in promoting AILI and provide new insights into immune modulation of the disease pathogenesis. [ABSTRACT FROM AUTHOR]

• This review summarized the mechanism of CXCR6/CXCL16 axis in the pathological process of autoimmune diseases. • The CXCR6/CXCL16 axis is a promising therapeutic target for human autoimmune diseases. The C–X–C motif ligand 16, or CXCL16, is a chemokine that belongs to the ELR − CXC subfamily. Its function is to bind to the chemokine receptor CXCR6, which is a G protein-coupled receptor with 7 transmembrane domains. The CXCR6/CXCL16 axis has been linked to the development of numerous autoimmune diseases and is connected to clinical parameters that reflect disease severity, activity, and prognosis in conditions such as multiple sclerosis, autoimmune hepatitis, rheumatoid arthritis, Crohn's disease, and psoriasis. CXCL16 is expressed in various immune cells, such as dendritic cells, monocytes, macrophages, and B cells. During autoimmune diseases, CXCL16 can facilitate the adhesion of immune cells like monocytes, T cells, NKT cells, and others to endothelial cells and dendritic cells. Additionally, sCXCL16 can regulate the migration of CXCR6-expressing leukocytes, which includes CD8+ T cells, CD4+ T cells, NK cells, constant natural killer T cells, plasma cells, and monocytes. Further investigation is required to comprehend the intricate interactions between chemokines and the pathogenesis of autoimmune diseases. It remains to be seen whether the CXCR6/CXCL16 axis represents a new target for the treatment of these conditions. [ABSTRACT FROM AUTHOR]

• CD226 expression was up-regulated on NK cells and T cell subsets in tuberculosis patients. • CD226+-CD3+CD8+ T cells might be a potential predictor of tuberculosis occurrence. • CD226+-CD3+CD4+ T cells and -CD56dimCD16+ NK cells displayed a higher level of IFN-γ, and CD226+-CD3+CD4+, -CD3+CD8+T cells and -CD56dimCD16+ NK cells displayed a higher level of CD107a production from tuberculosis patients. • CD226+-CD3+CD4+ T cells and CD56dimCD16+ NK cells tended to mediate cytotoxicity for disease progression. Human T cells and natural killer (NK) cells are major effector cells of innate immunity exerting potential immune surveillance against tuberculosis infection. CD226 is an activating receptor playing vital roles in the functions of T cells and NK cells during HIV infection and tumorigenesis. However, CD226 is a less-studied activating receptor during Mycobacterium tuberculosis (Mtb) infection. In this study, we used peripheral blood from tuberculosis patients and healthy donors to evaluate CD226 immunoregulation functions from two independent cohorts using Flow cytometry. Here, we found that a subset of T cells and NK cells that constitutively express CD226 exhibit a distinct phenotype in TB patients. In fact, the proportions of CD226+ and CD226- cell subsets differ between healthy people and tuberculosis patients, and the expression of immune checkpoint molecules (TIGIT, NKG2A) and adhesion molecules (CD2, CD11a) in CD226+ and CD226- subsets of T cells and NK cells exhibits special regulatory roles. Furthermore, CD226+ subsets produced more IFN-γ and CD107a than CD226- subsets in tuberculosis patients. Our results imply that CD226 may be a potential predictor of disease progression and clinical efficacy in tuberculosis by mediating the cytotoxic capacity of T cells and NK cells. [ABSTRACT FROM AUTHOR]

• A relevant study analysis in clinical trials was conducted, all of which showed that the model had good stability and potential application value for predicting outcomes. • The correlation between immune landscape and risk score and CPT1B was identified. We identified the drugs which patients are more likely to benefit from. • We performed the relevant basic assay validation for CPT1B, and the proliferation ability of RCC cells was inhibited after the knockdown of protein expression of CPT1B. • In conclusion, we established a four-gene model that can predict prognosis of RCC with potential applications in diagnosis and clinical treatment. Three subtypes of samples were generated based on genes involved in fatty acid metabolism in The Cancer Genome Atlas (TCGA)-RCC patients using a non-negative matrix factorization (NMF) algorithm. 32 co-expressed modules were identified using WCGNA. We constructed a four-gene signature in our training set using least absolute shrinkage selection operator regression analysis and verified it in our testing and overall sets. A relevant study analysis in clinical trials was conducted, which showed the model had good stability and potential application value for predicting outcomes. We analyzed the immune microenvironment using MCPcounter , CIBERSORT, quanTIseq, TIMER and ESTIMATE algorithms, and the result indicated risk was positively related to T cells, B-lineage, and fibroblasts and negatively correlated with monocytic lineage, myeloid dendritic cells, neutrophils, and endothelial cells, and CPT1B was positively related to T cells, CD8 + T cells, Cytotoxic lymphocytes and NK cells, and negatively correlated with myeloid dendritic cells, fibroblasts, endothelial cells. Tumor mutation burden was positively related to risk score and the expression of CPT1B using the R packages corrplot , circlize. Through the R package pRRophetic, drug sensitivity tests showed that the low-risk score group would benefit more from sunitinib and less from pazopanib, sorafenib, temsirolimus, gemcitabine and doxorubicin than the high-risk score group. We performed the relevant basic assay validation for CPT1B, and the proliferation ability of RCC cells was inhibited after the knockdown of protein expression of CPT1B. In conclusion, we established a four-gene model that can predict outcomes of RCC with potential applications in diagnosis and treatment. [ABSTRACT FROM AUTHOR]

• The metabolic reprogramming of NK cells plays an important role in liver cancer. • Immune and metabolic checkpoints are believed to interact in the functioning of the NK cells. • Targeting NK cell immunometabolism will be the promising treatment strategy. Natural killer (NK) cells are being used effectively as a potential candidate in tumor immunotherapy. However, the migration and transport of NK cells to solid tumors is inadequate. NK cell dysfunction, tumor invasiveness, and metastasis are associated with altered metabolism of NK cells in the liver cancer microenvironment. However, in liver cancers, metabolic impairment of NK cells is still not understood fully. Evidence from various sources has shown that the interaction of NK cell's immune checkpoints with its metabolic checkpoints is responsible for the regulation of the development and function of these cells. How immune checkpoints contribute to metabolic programming is still not fully understood, and how this can be beneficial needs a better understanding, but they are emerging to be incredibly compelling to rebuilding the function of NK cells in the tumor. It is expected to represent a potential aim that focuses on improving the efficacy of therapies based on NK cells for treating liver cancer. Here, the recent advancements made to understand the NK cell's metabolic reprogramming in liver cancer have been summarized, along with the possible interplay between the immune and the metabolic checkpoints in NK cell function. Finally, an overview of some potential metabolic-related targets that can be used for liver cancer therapy treatment has been presented. [ABSTRACT FROM AUTHOR]

• Immune system roles in the anti-prion action of cellulose ether (CE) are unknown. • CE effect is impaired by pre T-cell antigen receptor α deficiency or thymectomy. • CE effect is also impaired by TCRδ deficiency or lytic granule dysfunction. • The αβ T-cell lineage, B cells or TLR4 signaling pathway do not affect CE effect. • Interaction between NKT and γδ T cells may be involved in the action of CE. The anti-prion activity of cellulose ether (CE) has been reported in rodents, but the mechanism of action is not well understood. As defects in early T-cell development have been reported in Tga20 mice which show only a slight effect of CE administration, we investigated the involvement of immune functions in the CE action. We confirmed an insertion of the prion protein transgene into the pre T-cell antigen receptor α gene of Tga20 mice, and its impaired expression in the thymus and other tissues. The influence of immune suppression on the CE effect was then examined in high CE-responder mice treated with immunosuppressive agents or neonatal thymectomy. As neonatal thymectomy significantly reduced the CE effect, we compared the influence of various T-cell defects in mice with similar genetic backgrounds. The CE effect was increased or unchanged in mice with defects in the αβ T-cell lineage, whereas it was abolished in T-cell receptor δ deficient mice. Further, when other immune defects were examined, the CE effect was reduced in mice with lysosomal trafficking dysfunction, but was unchanged in mice deficient in B-cell differentiation or toll-like receptor 4 signaling. These findings collectively suggest that the mechanism of CE action may involve γδ T cells and lytic granule function, as well as immune factors like natural killer T cells which are lacking in pre T-cell antigen receptor α deficient mice and neonatally thymectomized mice. [ABSTRACT FROM AUTHOR]

• The immune microenvironment is emerging as a determinant of cervical cancer treatment. • The expression of B cells and PD-L1 increased after treatment with PD-1 inhibitors. • B cells may play a role in cervical cancer immunotherapy. This study evaluated the basic immune status of cervical cancer and the influences of immunotherapy on the immune microenvironment, and analyzed the correlation between changes in the immune microenvironment and prognosis. We retrospectively analyzed the treatment status of 8 patients with advanced recurrent cervical cancer treated with PD-1 inhibitors and detected the tumor-infiltrating immune markers (CD3, CD4, CD8, CD20, CD56, CD68, PD-1, and PD-L1) by immunohistochemistry. All patients showed good tolerance during the treatment. Complete response (CR), partial response (PR) and stable disease (SD) was observed in 3, 2, and 3 patients, respectively. Immunohistochemical analysis showed immunotherapy resulted in increased infiltration of T lymphocytes, natural killer cells, and B cells, especially among those who responded well. The expression of B cells in 4 of the 5 patients with clinical benefit was relatively high, and the expression of PD-L1 in these 5 patients showed a combined positive score > 3. PD-L1 expression increased significantly after treatment with PD-1 inhibitors. Second-generation sequencing showed that the tumor mutation burden of two patients with adenocarcinoma was high, and after immunotherapy, one case recurred after cure and the other remained stable. PR was also observed in squamous cell carcinoma patients with dMMR (p.R2165H/c.6494G > A) and PIK3CA (p.E545K(E9)) mutations. The expression of B cells and PD-L1 has certain predictive effect for the efficacy of immunotherapy in cervical cancer under the condition of high or low T cell infiltration, and can inform treatment decision-making for patients with advanced cervical cancer. [ABSTRACT FROM AUTHOR]

• Clinical grade NK cells can be obtained from different sources. • CAR NK cell therapy cause ADCC-dependent cytotoxicity against tumor cells. • CAR-NK cell therapy causes no on-target, off-tumor toxicity. CAR-T (chimeric antigen receptor T cell) technology, which has recently showed successful results in the treatment of hematological tumors, has been the focus of attention as one of the most potent approaches in tumor immunotherapy. However, side effects and limitations of this application, such as the risk of graft versus host disease (GvHD), make it challenging to be as accessible as other treatments. Natural killer cells (NK) could be transplanted without alloreactivity, making them as an off-the-shelf product. CAR-NK (chimeric antigen receptor NK cell) therapy can circumvent some serious limitations of CAR-T cell therapy. Application of CAR-NK cells have some considerable advantages over CAR-T cells. These include lack of cytokine release syndrome (CRS), neurotoxicity, and G v HD when using allogenic CAR-T cell. These features lessen the risk of tumor antigen loss and disease relapse. Moreover, NK cells which were derived from different sources, can make the CAR therapy more feasible. In this narrative review, we outlined the key features of CAR-NK cells as an alternative to CAR-T cell therapy in cancer immunotherapy and highlighted the main advantages. [ABSTRACT FROM AUTHOR]

• Interleukin-17 is a proinflammatory cytokine involved in chronic inflammation. • Interleukin-17 is involved in the pathogenesis of various immune-mediated diseases. • Several IL-17 and IL-17R inhibitors were approved to treat some immune-mediated diseases. • Ixekizumab, Secukinumab, and Brodalumab monoclonal antibodies target IL-17A and IL-17R. • Ixekizumab, Secukinumab, and Brodalumab are extremely effective to treat Psoriasis. Interleukin-17 (IL-17) is a proinflammatory cytokine involved in chronic inflammation occurring during the pathogenesis of allergy, malignancy, and autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, and psoriasis. IL-17 is produced by multiple cell types of adaptive and innate immunity, including T helper 17 cells, CD8 + T cells, γδ T cells, natural killer T cells, and innate lymphoid cells. Monoclonal antibodies (mAbs) targeting IL-17 and/or IL-17R would be a potential approach to study this therapeutic tool for these diseases. In the current review, we aimed to highlight the characteristics of IL-17 and its important role in the pathogenesis of related diseases. Critical evaluation of the mAbs targeting IL-17A and IL-17 receptors (e.g., Ixekizumab, Secukinumab, and Brodalumab) in various immune-mediated diseases will be provided, and finally, their clinical efficacy and safety will be reported. [ABSTRACT FROM AUTHOR]

• Macrophages and NK cells exert both immunostimulation and immunosuppression in TME. • TAMs communicate with NK cells by soluble mediators and cell-to-cell interactions. • Macrophage/NK cell-based therapies shed new perspectives in cancer immunotherapy. The tumor microenvironment (TME) is jointly constructed by a variety of cell types, including tumor cells, immune cells, fibroblasts, and epithelial cells, among others. The cells within the TME interact with each other and with tumor cells to influence tumor development and progression. As the most abundant immune cells in the TME, macrophages regulate the immune network by not only secreting a large amount of versatile cytokines but also expressing a series of ligands or receptors on the surface to interact with other cells directly. Due to their strong plasticity, they exert both immunostimulatory and immunosuppressive effects in the complex TME. The major effector cells of the immune system that directly target cancer cells include but are not limited to natural killer cells (NKs), dendritic cells (DCs), macrophages, polymorphonuclear leukocytes, mast cells, and cytotoxic T lymphocytes (CTLs). Among them, NK cells are the predominant innate lymphocyte subsets that mediate antitumor and antiviral responses. The activation and inhibition of NK cells are regulated by cytokines and the balance between activating and inhibitory receptors. There is an inextricable regulatory relationship between macrophages and NK cells. Herein, we systematically elaborate on the regulatory network between macrophages and NK cells through soluble mediator crosstalk and cell-to-cell interactions. We believe that a better understanding of the crosstalk between macrophages and NKs in the TME will benefit the development of novel macrophage- or NK cell-focused therapeutic strategies with superior efficacies in cancer therapy. [ABSTRACT FROM AUTHOR]

• Low frequency, exhausted immune status of CD56dim NK cell in (EV71+) severe patients. • The cytotoxic functions of CD56dim NK cells were significantly enhanced in mild patients. • Enhanced IL-10 production secretion of CD56bright NK cells in mild case. • Robust TNF-α(and IL-10) secretion of CD56bright NK cells in (EV71+) severe patients. • The frequency and functional status of NK subsets were closed related to the prognosis of HFMD. The roles of CD56bright and CD56dim natural killer (NK) subsets in the viral clearance and inflammatory processes of hand, foot, and mouth disease (HFMD) remain undefined. A total of 39 HCs and 55 patients were enrolled to analyze peripheral CD56bright and CD56dim NK cells according to cell number, surface receptors, cytotoxic activities, and cytokine production. The plasma concentrations of IL-2, IL-6, IL-10, IFN-γ, TNF-α,and MCP-1 were detected using ELSA. Peripheral blood NK cells was significantly lower in severe patients than in HCs due to the dramatic loss of CD56dim NK cells with no changes in the cell count of CD56bright NK cells. For mild patients, decreased NKp46 expression coincided with enhanced cytolysis (CD107a, GNLY, and GrB) in CD56dim NK cells and decreased NKG2A expression with enhanced IL-10 production in CD56bright NK cells. In contrast, severe patients showed the dominant expression of NKG2A and decreased expression of NKG2D accompanied by cytotoxic dysfunction in CD56dim NK cells. Imbalanced receptor expression coincided with the increased concentrations of TNF-α in CD56bright NK cells. Moreover, EV71+ patients showed significantly decreased counts of CD56dim NK cells with cytolysis dysfunction, displayed cytokine hypersecretion in CD56bright NK cells, while the EV71− patients displayed significantly higher plasma cytokine concentrations. The changes in the immune function of NK subsets and their subpopulations were closely related to clinical inflammatory parameters. Low-frequency, exhausted immune status of CD56dim NK cells and disordered inflammatory cytokine secretion of CD56bright NK cells were associated with the progression of severe HFMD, especially in EV71-infected patients. This promoted the severity of inflammatory disorders, leading to enhanced disease pathogenesis. [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]

• miR-155 is expressed by immune cells and infected cells during viral infections. • miR-155 strongly affects both anti-virus innate and adaptive immune responses. • Irregular miR-155 expression supports virus persistence and pathologic reactions. • miR-155 may be a possible therapeutic target for treatment of viral diseases. The microRNA, miR-155 regulates both adaptive and innate immune responses. In viral infections, miR-155 can affect both innate immunity (interferon response, natural killer cell activity, and macrophage polarization) and adaptive immunity (including generation of anti-viral antibodies, CD8+ cytotoxic T lymphocytes, Th17, Th2, Th1, Tfh and Treg cells). In many viral infections, the proper and timely regulation of miR-155 expression is critical for the induction of an effective anti-virus immune response and viral clearance without any harmful immunopathologic consequences. MiR-155 may also exert pro-viral effects, mainly through the inhibition of the anti-viral interferon response. Thus, dysregulated expression of miR-155 can result in virus persistence and disruption of the normal response to viral infections. This review provides a thorough discussion of the role of miR-155 in immune responses and immunopathologic reactions during viral infections, and highlights its potential as a therapeutic target. [ABSTRACT FROM AUTHOR]

• Galectin-9 is involved in the opsonisation of Gram-negative bacteria. • Galectin-9 promotes anti-bacterial immune defence. • Galectin-9 suppresses cytotoxic T cell function. • This effect can be achieved by "opsonisation" of T cells by galectin-9. • Affected apoptotic T cells can be phagocytosed by macrophages. Galectin-9 is a member of the galectin family of proteins, which were first identified to specifically bind to carbohydrates containing β-galactosides. Galectin-9 is conserved through evolution and recent evidence demonstrated its involvement in innate immune reactions to bacterial infections as well as the suppression of cytotoxic immune responses of T and natural killer cells. However, the molecular mechanisms underlying such differential immunological functions of galectin-9 remain largely unknown. In this work we confirmed that soluble galectin-9 derived from macrophages binds to Gram-negative bacteria by interacting with lipopolysaccharide (LPS), which forms their cell wall. This opsonisation effect most likely interferes with the mobility of bacteria leading to their phagocytosis by innate immune cells. Galectin-9-dependent opsonisation also promotes the innate immune reactions of macrophages to these bacteria and significantly enhances the production of pro-inflammatory cytokines – interleukin (IL) 6, IL-1β and tumour necrosis factor alpha (TNF-α). In contrast, galectin-9 did not bind peptidoglycan (PGN), which forms the cell wall of Gram-positive bacteria. Moreover, galectin-9 associated with cellular surfaces (studied in primary human embryonic cells) was not involved in the interaction with bacteria or bacterial colonisation. However, galectin-9 expressed on the surface of primary human embryonic cells, as well as soluble forms of galectin-9, were able to target T lymphocytes and caused apoptosis in T cells expressing granzyme B. Furthermore, "opsonisation" of T cells by galectin-9 led to the translocation of phosphatidylserine onto the cell surface and subsequent phagocytosis by macrophages through Tim-3, the receptor, which recognises both galectin-9 and phosphatidylserine as ligands. [ABSTRACT FROM AUTHOR]

• Tumor includes a wide range of cancer and non-cancer cells that play key roles in the tumor growth. • CD4+ and CD8+ lymphocytes, and NK cells provide anti-tumor immunity, while macrophages, Tregs and CAFs promote tumor growth. • Resveratrol affect both anti-tumor and tumor-promoting cells in tumor, leading to activation of anti-tumor immunity. • Resveratrol can suppress hypoxia and angiogenesis through modulation of intercellular communications within tumor microenvironment. Tumor resistance to therapy modalities is one of the major challenges to the eradication of cancer cells and complete treatment. Tumor includes a wide range of cancer and non-cancer cells that play key roles in the proliferation of cancer cells and suppression of anti-tumor immunity. For overcoming tumor resistance to therapy, it is important to have in-depth knowledge relating to intercellular communications within the tumor microenvironment (TME). TME includes various types of immune cells such as CD4 + T lymphocytes, cytotoxic T lymphocytes (CTLs), natural killer (NK) cells, macrophages, and T regulatory cells (Tregs). Furthermore, some non-immune cells like cancer stem cells (CSCs), mesenchymal stem cells (MSCs), and cancer-associated fibroblasts (CAFs) are involved in the promotion of tumor growth. The interactions between these cells with cancer cells play a key role in tumor growth or inhibition. Resveratrol as a natural agent has shown the ability to modulate the immune system to potentiate anti-tumor immunity and also help to attenuate cancer cells and CSCs resistance. Thus, this review explains how resveratrol can modulate interactions within TME. [ABSTRACT FROM AUTHOR]