IL2 expression

We found that all three TCRs in each patient could specifically identify corresponding ATCs. In conclusion, we established an efficient approach to isolate tumour-reactive TCRs based on combinations of multiple activation and effector molecules through single-cell RNA sequencing.

In particular, NKp30a overexpression in NK92 cells improved the clearance of THP-1 cells in vivo without IL-2 supplementation. Collectively, our results highlight the distinct role of IL-2 in the regulation of NKp30 compared to that of NKp46 and suggest NKp30 upregulation, as shown here by ectopic overexpression, as a viable modality to harness NK cells in cancer immunotherapy, possibly in combination with IL-2 immunocytokines.

Our findings illustrate that G47Δ-mIL2 is efficacious, stimulates antitumor immunity against orthotopic GBM, and may also target GSC. OHSV expressing IL-2 may represent an agent that merits further exploration in patients with GBM.

These findings highlight the multifaceted roles of CD81 and CD82 in T cell activation, cytokine production, memory subset accumulation, and target cell cytolysis. Therefore, these findings suggest the potential of CD81 and CD82 as promising candidates for co-stimulatory molecules in immune therapeutic strategies for cancer treatment within the intricate TME.

Moreover, the observed downregulation of ARG1 expression indicates a transition in the tumor microenvironment from an immunosuppressive state to an antitumor state following treatment with CFCFB. The upregulation of IL-2 and CD8 expression facilitated the differentiation of effector T cells, resulting in an augmented population of CD8+ T cells, thereby indicating the activation of systemic immune response.

We also demonstrated that Rta-induced PD-L1 expressions could impair interleukin 2 secretion of T cells, and this mechanism may be through ERK activation. These results displayed the importance of EBV Rta in PD-L1 expression in NPC and may give an alternative target for NPC therapy.

Since IL-2 can be trans-presented via CD25 to another cell, CD25+AML cells may deliver environmental IL-2 to surrounding immune cells to produce myeloid growth factors for their proliferation. We hypothesize that cellular interactions via IL-2/CD25 axis in the bone marrow microenvironment contributes to the growth advantage of these AML cells and affects the clinical outcome of those AML patients.

Further evaluations indicated that the U-101-LNP/IL-2F mRNA group maintained proper levels of inflammatory factors without obvious alterations in liver and renal functions. Taken together, the U-101-LNP/IL-2F mRNA formulation demonstrated effective antitumor activity and safety, which suggests potential applicability in clinical immunotherapy.

YQ was the key disassembled prescription of YQYYJD, exerting significant antitumor effects and immune regulation effects on NSCLC. It may have relieved T cell exhaustion and regulated the immune microenvironment to exert antitumor effects by changing lung cancer-related targets, pathways, and biological processes.

To sum up, the occurrence and development of AR induced by OVA and pollen of Artemisia annua, Artemisia argyi and Artemisia Sieversiana were related to TLR4/MyD88 signal pathway.

BMSC can promote the drug resistance of leukemia cells, and TET may reverse the BMSC-mediated drug resistance via inhibiting IL-6/STAT3 signaling pathway.

Finally, we find that Aiolos, a related Ikaros family member and known CD4-CTL antagonist, represses Eos expression by antagonizing STAT5-dependent activation of the Ikzf4 promoter. Collectively, our findings reveal a mechanism wherein Eos and Aiolos act in opposition to regulate cytotoxic programming of CD4+ T cells.

PICRUSt results showed that LTE300 was significantly (P < 0.05) enriched in four pathway pathways at KEGG level 2. In conclusion, dietary supplementation with LTE improved growth performance and intestinal health by enhancing antioxidant capacity, intestinal barrier and immune function, and regulating intestinal flora of yellow-feathered broilers.

to evaluate the interactions between immune system components of healthy individuals and EVs derived from monocytic and lymphoid lineage cells generated in the presence of baricitinib (BARI) and itacitinib (ITA) and their possible effects. The higher proportion of arachidonic acid in the FA content of ITA-L/M-EVs could be related to the thrombosis described in patients treated with ITA. EVs also induced a decrease in the respiratory burst of neutrophils.

Additionally, in vitro experiments confirmed that PF reduces the expression of PD-L1 in Huh-7 liver cancer cells by inhibiting NF-κB. PF plays a synergistic role of Sor inhibiting HCC progression by regulating the NF-κB/PD-L1 pathway.

In summary, Clostridium species represent a promising platform for cancer therapy, with potential for localised gene delivery and immunomodulation selectively within the tumour microenvironment. The ongoing clinical progress being made with C. novyi-NT, in addition to developments in genetic modification techniques and non-invasive imaging capabilities, are expected to further progress Clostridium as an option for cancer treatment.

Both in vitro and in vivo experiments verified that AIPH/Cu-Cys@Lipo significantly inhibited tumor development by decreasing mitochondrial membrane potential, activating CD4 and CD8 T cells and promoting the expression of IL-2 and TNF-α. AIPH/Cu-Cys@Lipo provides high-quality strategies for safe and effective tumor immunotherapy.

PTH regulates intestinal microbiota balance and restores mTreg cells to alleviate experimental AIH, which is closely related to the TLR/CXCL16/CXCR6/NF-κB signaling pathway.

This study marks a significant advance in the study of long non-coding RNAs in the immune system by ascribing cell-intrinsic, sequence-specific in vivo function to Malat1. These findings have implications for T cell-mediated autoimmune diseases, antiviral and anti-tumor immunity, as well as lung adenocarcinoma and other malignancies where Malat1 is overexpressed.

P1, N=60, Recruiting, DEKA Biosciences

These results indicate that switching of the splicing decision from flPD1 to ∆Ex3PD1 by targeting SRPK1 could represent a potential novel mechanism of immune checkpoint inhibition in cancer.

High cholesterol regulated the ERS-ERMC-mitophagy axis to induce the exhaustion of CD8 T cells in CRC.

DP-TILs may have superior T cell receptors recognizing tumor-antigens and contribute to tumor eradication, especially when administrated anti-CD39 antibody.

Adoptively transferred ThGM cells suppressed CRC growth whereas mTORC1 inhibition abolished this effect. mTORC1 is essential for the anti-CRC activity of ThGM cells.

The additive effect of the combined knockdown of tumor-intrinsic VISTA and CTLA-4 can substantially upregulate pro-inflammatory factors, downregulate anti-inflammatory factors, and inhibit tumor development in MCF7 cells. The significant positive correlation between VISTA and CTLA-4 in luminal A breast cancer might support the idea that a network of inhibitory immune checkpoint molecules regulates anti-tumoral immune responses; thus, combinational immune checkpoint molecules blockade can be suggested.

Additionally, CPG clearly enhanced B-cell-mediated humoral immunity and immune-cell-mediated cellular immunity, and, finally, induced S180 cell apoptosis by arresting cells in the G0/G1 phase, which might result from the IL-17 signaling pathway. These data may help to improve comprehension surrounding the roles of humoral and cellular immunity in anti-tumor immune responses.

Moreover, compared to the model group, CDBS significantly decreased leukocytes, lymphocytes, and neutrophils in the blood, as well as levels of IL-2, LTB4, 5-LO, NO, and ALOX5 expression in rat blood. Our findings suggest the therapeutic effect of CDBS on radiodermatitis by downregulating ALOX5 to inhibit inflammation, potentially serving as a radiodermatitis therapy.

However, compared to the EMB group, the oxidant indices and expression of genes related to ER stress, pyroptosis, and pro-inflammatory factors were significantly down-regulated (P < 0.05), whereas the antioxidant indicators and anti-inflammatory factor were significantly up-regulated in the EMB + RES group (P < 0.05). In conclusion, EMB caused hepatocytes pyroptosis and inflammation in grass carp, and RES could alleviate EMB-induced pyroptosis and inflammation in L8824 cells by ameliorating oxidative stress/ER stress.

In summary, our work suggests that AND-gate targeting can increase not just specificity, but potency, even against very low expression tumour targets in MM. Link to preprint https://doi.org/10.1101/2023.04.04.535580

In summary, OutSmart™ IL-2/15 is a genetic module that produces CD8-IL-2/15 in response to T cell activation, promoting robust CAR-T expansion and enhanced anti-tumor efficacy. Furthermore, local production of a CD8-IL-2/15 enhances the effector function of bystander CD8+ T cells and NK cells, but only minimally activates Treg cells due to removing the IL-2Rα binding interface. Inducible production of CD8-IL-2/15 dramatically improves the potency of a ROR1 CAR for treating ROR1+ solid and liquid cancers.

Image analysis revealed that TDB treatment induced T cell-mediated cytotoxicity in four patients, with sub-optimal TDB-induced cytotoxicity observed in two patients, highlighting intrinsic resistance mechanisms to TDB treatment and the need for greater mechanistic understanding. Notably, all patients' effector cells exhibited upregulation of CD69, a T cell activation marker, after 24 hours post-TDB treatment which was sustained for 72 hours. TDB treatment also led to the upregulation of CD25, starting at 24 hours and peaking 72 hours post-treatment.

These results suggest that IFN-γ and IL-21 contribute to the pathogenesis of IELCE, and IFN-γ may be involved in T-cell activation and mucosal injury in CE. STAT1 and STAT3 activation in ITCL cells suggests a role for the upregulation of the STAT pathway in the pathogenesis of ITCL.

The combination of these treatments may have an exceptional impact on future TNBC immunotherapeutic approaches by providing a powerful personalized medicine paradigm. Therefore, our findings have a great translational potential for improving outcomes in TNBC patients.

Our studies suggest that RAD21 protein and level of its post-translational modifications in the bone marrow cells may play a potential role in hematopoiesis. Overall, Rad21 haploinsufficiency impairs hematopoietic differentiation and increases HSC self-renewal.

Moreover, we find that blocking the specific receptor (PD-1) using antibodies significantly relieves the S. aureus-imposed inhibition. Our findings suggest that therapeutically targeting PD-1 is a possible future strategy for treating certain antibiotic-resistant staphylococcal infections.

Moxibustion with seed-size moxa cone can enhance the anti-tumor effect of CTX and improve the quality of life of HLCB mice, which may be related with its effect in activating the expressions of Caspase-3 and Caspase-9 in tumor tissue.

Background/Purpose: HRES-1/Rab4 (Rab4A) is a small GTPase that is overexpressed in SLE patient T cells 1,2 , mediates the enhanced recycling of CD3 and CD4 cell surface receptors 1,2 , and the activation of the mechanistic target of rapamycin (mTOR) 3... To understand the cellular consequences of Rab4A overexpression, our lab has created unique Rab4A-mutant Jurkat cell lines, which contain GFP-expressing vector alone (control), doxycycline-inducible vectors that overexpress Rab4A (Rab4A ++ ) or the dominant-negative mutant Rab4A S27N (Rab4A DN ) 8... The increased pAkt1 and p4EBP1 in SLE patients' CD38 + CD4 + T cells suggests that CD38 activates mTOR via Akt, coinciding with a recent finding of CD38/PI3K/Akt/mTOR axis in cervical cancer 10 . CD38 is an NAD + hydrolase, which regulates Sirtuin-1 activity, a NAD + -dependent histone deacetylase that suppresses STAT3 activity. STAT3 activation is also known to be regulated by mTOR 11–13 .

Furthermore, IL2 expression was positively correlated with PD-1, PD-L1, and CTLA-4 expression. Our results indicate that down-regulation of IL2 predicts poor prognosis and is associated with immune escape in LUAD, and IL2 could serve as a potential novel prognostic biomarker of LUAD.

These findings might offer a potential combined strategy for patients resistant to anti-PD therapy via combining FEN1 knockdown and PD-1 blockade.