The immunological pathways that cause Multisystem Inflammatory Syndrome after SARS-CoV-2 infection in children (MIS-C) remain under investigation. The aim of this study was to prospectively compare the T-cell cytokine expression profile between children with convalescent COVID-19 or MIS-C. Peripheral blood mononuclear cells (PBMCs) were isolated from unvaccinated children with acute MIS-C (MIS-C_A) before immunosuppression, convalescent MIS-C (one month after syndrome onset, MIS-C_C), convalescent COVID-19 (one month after hospitalization) and healthy, unvaccinated controls. Intracellular expression of IL-4, IL-2, IL-17, IFN-γ, TNF-α and Granzyme B, post SARS-CoV-2-Spike antigenic mix stimulation of T cell subsets was analyzed by 13-colour Flow Cytometry. Twenty children (4 MIS-C_A, 4 MIS-C_C, 8 post-COVID-19, and 4 controls) with median age (IQR): 11.5(7.25-14) years were included in the study. From the comparison of the flow cytometry analysis of the 14 markers of MIS-C_A with the other 3 groups (MIS-C_C, post-COVID-19 and controls), statistically significant differences were identified for: 1. CD4 +IL-17 +/million CD3 +: 293.0 (256.4-870.9) vs 50.7 (8.4-140.5); P-value:0.03, vs 96.7 (89.2-135.4); P-value:0.03 and vs 8.7 (0.0-82.4); P-value:0.03, respectively, 2. CD8 +IL-17 +/million CD3 +: 335.2 (225.8-429.9) vs 78.0 (31.9-128.9) vs 84.1(0.0-204.6) vs 33.2 (0.0-114.6); P-value:0.05, respectively 3. CD8 +IFN-γ +/million CD3 +: 162.2 (91.6-273.4) vs 41.5 (0.0-77.4); P-value:0.03 vs 30.3(0.0-92.8); P-value:0.08, respectively. In children presenting with MIS-C one month after COVID-19 infection, T cells were found to be polarized towards IL-17 and IFN-γ production compared to those with uncomplicated convalescent COVID-19, a finding that could provide possible immunological biomarkers for MIS-C detection.

Hepatocellular carcinoma (HCC) is the most prevalent form of primary liver cancer and ranks as the second leading cause of cancer-related mortality globally. Despite advances in current HCC treatment, it remains a malignancy with poor prognosis. Therefore, developing novel treatment options for patients with HCC is urgently needed. Chimeric antigen receptor (CAR)-modified natural killer (NK) cells have shown potent anti-tumor effects, making them as a promising immunotherapy strategy for cancer treatment. Glypican-3 (GPC3), a cell surface oncofetal glycoprotein, is highly expressed in most HCC tissues, but not in normal tissues, and functions as a key driver of carcinogenesis. Given its high expression level on the cell surface, GPC3 is considered as an attractive immunotherapy target for HCC. In this study, two GPC3-specific CAR-NK cells, NK92MI/NH3 and NK92MI/HS20, were established using NK92MI cells, a modified IL-2-independent NK cell line. These cell lines were engineered with third generation GPC3-specific CAR, and their activities were subsequently evaluated in the treatment of HCC. We found that NK92MI/NH3 cells, rather than NK92MI/HS20 cells, exhibited a significant cytotoxicity effect against GPC3 + HepG2 cells in vitro and efficiently suppressed tumor growth in a xenograft model using NSG mice. In addition, irradiated NK92MI/NH3 cells displayed similar anti-tumor efficacy to unirradiated NK92MI/NH3 cells. Furthermore, we observed that NK92MI/NH3 cells showed higher killing activity against the GPC3 isoform 2 overexpression cell line (SK-Hep1-v2) than those with GPC3 isoform 1 overexpression cell line (SK-Hep1-v1) both in vitro and in vivo. This suggest that the presence of different GPC3 isoforms in HCC may impact the cytotoxicity activity of NK92MI/NH3 cells and potentially influence therapeutic outcomes. These findings highlight the effective anti-HCC effects of NK92MI/HN3 cells, as well as the underlying therapy resistance, suggesting their potential as a promising therapy for HCC.

Motivation: Cancer, a leading cause of death worldwide, is intertwined with immune system. Changing the state of immune system, as a complex network of cells and molecules interacting in a hierarchical mode, holds considerable fascination to fight cancer. This alteration can involve debilitating pro-tumorigenic and reinvigorating anti-tumorigenic functions by the help of driver vertices. The utilization of network controllability and control centrality-based analysis will aid in the identification of driver vertices to control target proteins that play significant roles in the anti-tumorigenic and pro-tumorigenic functions of immune cells. In this study, a weighted generalization of the control centrality was constructed, in which the control power of each vertex in the network is obtained based on the importance of a set of under control vertices. Results: Screening all homo sapiens-related pathways in KEGG database, we find that “Immune and cancer pathways” subnetwork showed the greatest number of edges and nodes in relation to positive and negative target proteins. The first five driver vertices obtained for positive targets are ICAM2, TLR2, MAP2K4, ELK1, SIRT1 and for negative targets are ELK4, RBX1, NFATC1, NFATC2, NFATC3. Our results suggest that exposing the external signal to reinvigorate driver vertices of positive targets and debilitate driver vertices of negative target will result in changing the immune system state to fight cancer.

Rheumatoid arthritis (RA) is a systemic autoimmune disease driven by highly active autoantibody producing B cells. These B cells can be supported within ectopic germinal centers found in afflicted joints. Fibroblast like synoviocytes (FLS) present in inflamed joints support B cell survival, activation and differentiation. CD27 + memory B cells and naïve B cells show very distinct reactions to activation, particularly by CD40 ligand (CD40L). We show that FLS dependent activation of human B cells is dependent on interleukin 6 (IL-6) and CD40L. FLS have been shown to activate naïve as well as memory B cells. If the activatory potential of FLS is different for naïve and memory B cells had not yet been investigated. Our results suggest that FLS-induced activation of B cells is dependent on IL-6 and CD40L. While FLS are capable of inducing differentiation, isotype switching and antibody production in memory B cells, FLS capability to activate naive B cells is significantly lower.

The emergence of 16S rRNA and metagenomic sequencing has gradually revealed the close relationship between dysbiosis and colorectal cancer (CRC). Recent studies have confirmed that intestinal dysbiosis plays various roles in the occurrence, development, and therapeutic response of CRC. Perturbation of host immunity is one of the key mechanisms. Intestinal flora, or specific bacterium and its metabolites can modulate the progression of CRC through Toll-like receptors signaling, or via the recruitment, polarization and activation of innate and adaptive immune cells to reshape the pro-/anti-tumor microenvironment. On this basis, administration of gut bacteria to enhance immune homeostasis represents new cues for the treatment of CRC. In this review, we will cover the recent studies on the role of gut bacteria in the progression and treatment of CRC through immune response orchestration, which potentially offers insights for subsequent transformative research.

Hepatocellular carcinoma (HCC) represents a significant global cause of cancer-related mortality. Hepatitis B virus (HBV)infection is a major etiologic factor leading to HCC. While noteworthy progress has been made in managing HBV replication, achieving a cure for HBV-related HCC (HBV-HCC) remains challenging, and the overall survival outcome for HCC remains suboptimal. HBV persistence is attributed to a myriad of mechanisms, encompassing both innate and adaptive immune responses. Regulatory T cells(Tregs) are pivotal in upholding immune tolerance and modulating excessive immune activation. During HBV infection, Tregs mediate specific T cell suppression, thereby contributing to both persistent infection and the mitigation of liver inflammatory responses. Studies have demonstrated an augmented expression of circulating and intrahepatic Tregs in HBV-HCC, which correlates with impaired CD8 + T cells function. Consequently, Tregs play a dual role in the context of HBV infection and the progression of HBV-HCC. In this comprehensive review, we discuss pertinent studies concerning Tregs in HBV infection, HBV-related cirrhosis and HCC. Furthermore, we provide valuable treatment strategies pertinent to liver cancer management.