CSF2 expression

NOG (NOD/Shi- scid /IL-2R null ) and NOG-EXL (huGM-CSF/huIL-3 NOG) mice conditioned with Busulfan underwent i.v. injection of human CD34+ cells...In this context, animal models that recapitulate human disease are greatly needed. Leveraging xenograft tumors derived from patients with advanced HCCs and a commercially available immunodeficient mouse strain that expresses human GM-CSF and IL-3, we demonstrate a novel but accessible approach for modeling the HCC tumor microenvironment.

Assessment of M-MDSCs frequency holds promise as a predictive marker for disease progression and therapy response of coronary artery stenosis. The elevated presence of M-MDSCs suggests their potential role in modulating ACS-related inflammation.

MTX treatment induces secretion of IL-1 from activated RA-FLS which by autocrine signaling augments their release of GM-CSF. This unexpected effect of MTX might contribute to the persistence of synovitis.

UC-PDX-LN1, originating from bladder cancer, exhibited two druggable targets - HRAS and ERCC2 - responding well to chemotherapy and targeted therapy, though not to tipifarnib, an HRAS inhibitor...Clinical observations in bladder cancer patients revealed PNL in 1.61% of cases (35/2162) with associated poor prognosis. These findings propose a novel approach, advocating for the combination of anticancer/NETosis/thrombosis strategies for managing UC patients presenting with PNL in clinical settings.

By leveraging information within the signatures, we discover that the HB-EGF/EGFR/MAPK axis represents a hub of tumor-stroma crosstalk, promoting the expression of CSF2 and LIF and favoring the recruitment of macrophages. Together, these analyses demonstrate the utility of our approach for interrogating the extent and consequences of TME crosstalk.

We demonstrated CCL5 and CSF2 as potential novel biomarkers for predicting the response to ICIs in patients with UC and ESCC. The predictive value of these biomarkers in other cancer types warrants further evaluation in future studies.

SBWD may exert an anti-infection effect on LRTI by targeting IL-17A and GM-CSF through respiratory microbiota regulation. The mechanism of S. baicalensis action on respiratory microbiota in LRTI treatment merits further investigation.

Partial inhibition of OXPHOS or ATP-signaling including with BTK inhibition resulted in an anti-inflammatory B cell cytokine shift, reversed the B cell cytokine imbalance in patients with MS, and ameliorated neuroinflammation in a myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalitis mouse model. Our study identifies how pro- and anti-inflammatory cytokines are metabolically regulated in B cells and identifies ATP and its metabolites as a "fourth signal" that shapes B cell responses and is a potential target for restoring the B cell cytokine balance in autoimmune diseases.

Our co-culture system revealed the non-cell autonomous adverse effects of GM-CSF MΦ in individuals with ASD on neurons, mediated by interleukin-1α and TNF-α. These results may support the immune dysfunction hypothesis of ASD, providing new insights into its pathology.

DelNS1-GM-CSF displayed potent oncolytic activity against HCC and stimulated intra-tumor T-cell infiltration through activation of the JAK2-STAT3 pathway. Combination therapy with delNS1-GM-CSF and PD-1 blockade represents a promising immunotherapeutic strategy for HCC.

The autocrine cytokines, including GM-CSF, LIF, and OSM, contribute to constitutive STAT3/5 activation in TF-1(R140Q) cells, thereby modulating IDH2/R140Q-mediated malignant proliferation in TF-1 cells. Targeting STAT3/5 phosphorylation may be a novel strategy for the treatment of AML in patients harboring the IDH2/R140Q mutation. Video Abstract.

As a result, TAM induced by EBV abortive lytic cycle promotes NPC angiogenesis, invasion, and migration. Overall, this study elucidated the role of the EBV lytic life cycle in the late development of NPC and revealed a mechanism underlying the ZTA-mediated establishment of the tumor microenvironment (TME) that promotes NPC late-stage progression.

RADD demonstrates the ability to determine a quantitative analysis of DNA damage and repair in ovarian cancer samples. Considering its rapid turnaround time and correlation with HR status, RADD has potential use in determining clinical trial candidates stratified by HR status. Additionally, RADD correlates with known predictive biomarker CD39 for response with immunotherapy.

Exploratory outcome measures include patient-reported quality of life, biomarker analyses, coxsackie adenovirus receptor and E2F promoter expression, neutralizing antibodies, and markers of immunogenicity. Clinical trial information: Pending.

Safety will be assessed by physical examination, clinical laboratory evaluations, vital signs, and monitoring for adverse events (AEs; including serious AEs). Clinical trial information: NCT05733611.

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

In summary, ThGM cells in the PF and ELs might exacerbate endometriotic inflammation. IL-35 might suppress the function of ThGM cells via IL-35R.

Ovine IFN-τ may be an effective immunotherapeutic cytokine for the treatment of TNBC.

The use of UCB CD34+ HSCs to generate ILC1s, especially after being engineered with a CAR, could allow for a readily available supply of ILC1s to be produced for human adoptive transfer studies. Our findings provide evidence that targeting human ILC1s may be a promising therapeutic approach for extending disease-free survival in patients with AML.

To summarize, we show that normal myeloid cells have beneficial effects on CAR T cell function, and targeting these same myeloid cells is detrimental to CAR T cell activity. These findings provide insight into the reason for suboptimal CAR T cell activity in AML, and show that independent of target antigen and CAR construct, the nature of the cells being targeted can change the effectiveness of this therapy.

Targeting this axis diminished the neurotoxicity associated with this therapy. This study provides a rationale for testing TAK1-inhibition in a clinical trial for treating CD19 CAR-T cell-induced neurotoxicity.

A total of 91 pts are included in this analysis (initial melanoma cohort, 16 pts; R-D cohort, 75 pts; data cut: Dec 30, 2022). The overall objective response rate (ORR) was 37.4% (initial cohort, 37.5%; R-D cohort, 37.3%), and 18.7% of pts achieved complete response (CR; Table). The response rates seen were also encouraging when evaluated by prior anti–PD-1 therapy setting and disease stage (Table).

By contrast, DH82 cells lacked increased proliferation and motility. The significantly increased secretion of GM-CSF by persistently CDV-Ond-infected DH82 cells, the pH stability of this protein, and the lack of detrimental effects on DH82 cells renders this virus strain an interesting candidate for future studies aiming to enhance the oncolytic properties of CDV for the treatment of canine histiocytic sarcomas.

The most common treatment-related adverse event was pyrexia, with a Grade ≥ 3 of 13.3% in Arm A, 0% in Arm B,0% in Arm C, and 3.6% in Arm D. No Grade 5 events occurred in any of the study arms. Table: 1885P Summary of efficacy results Conclusions The combination immunotherapy of IV PV and cemiplimab demonstrated an acceptable safety profile and encouraging efficacy of ORR and survival with durable responses in patients with metastatic or unresectable RCC, regardless of previous ICI treatment.

In vivo activation of iNKT cells with αGalCer restored their anti-tumor functions suggesting that iNKT cells can be modulated to overcome CRC-associated pro-tumor phenotype. CRC patients' survival analyses demonstrated that tumor co-infiltration by iNKT cells and neutrophils correlates with negative clinical outcomes.ConclusionOur results reveal a functional plasticity of human intestinal iNKT cells in CRC, suggesting a pivotal role of iNKT cells in shaping the TME and cancer developmental trajectory with implications for treatment of CRC.

Tumor co-infiltration by iNKT cells and neutrophils correlates with negative clinical outcomes highlighting the importance of iNKT cells in the pathophysiology of CRC. Our results reveal a functional plasticity of iNKT cells in CRC suggesting a pivotal role of iNKT cells in shaping the TME with relevant implications for treatment.

NSA should be considered for application to investigational targeted therapies in order to identify populations most likely to benefit from treatment, in preparation for efficacy conclusive trials.

AE severity will be evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0.Clinical trial identification: NCT05733611.Editorial acknowledgement: Medical writing and editorial support were provided by Marita Chakhtoura, PhD, of AlphaBioCom, LLC, a Red Nucleus Company (King of Prussia, PA, USA) and were funded by Replimune Inc. (Woburn, MA, USA).Legal entity responsible for the study: Replimune Inc.

The median PFS was 7 months (range: 3- 18; Trabectedin alone for LMS= 4.3 mos; Dacarbazine alone = 1.6 mos); 6-month PFS rate, 55%; median OS 18.2 months (range: 4- 32); 6-month OS rate, 91%. These results suggest that (1) By indirect comparison, the combination regimen using Talimogene laherparepvec, Nivolumab & Trabectedin may be more effective as second/third-line/fourth therapy for advanced leiomyosarcoma with manageable toxicity, (2) Response is not related to PD-L1 positivity and (3) The best responders are patients with HR+ uterine LMS.

Reduction of GM-CSF in CAR-T cells could decrease the level of several proinflammatory cytokines without hampering the killing capacity. The manufacture of GM-CSF knockdown CAR-T cells does not require complicated transfections, which makes it more practical and feasible for clinical application.

RP1+nivo induced deep and durable antitumor activity in patients with advanced skin cancers, including anti–PD-1 and anti–PD-1/anti–CTLA-4–failed melanoma. The combination was generally well tolerated, consistent with prior data. Enrollment into a registration-directed cohort of patients with anti–PD-1–failed cutaneous melanoma (n=125) and a cohort with anti–PD-1–failed NMSC (n=30) is ongoing.

This initial data on the efficacy and safety of CG0070 plus pembrolizumab for the treatment of BCG unresponsive NMIBC is encouraging. Data on efficacy and safety for all enrolled patients, N=35, as well as biomarker (CAR, E2F, and PDL1) assessment will be presented at the time of the conference.

Our study demonstrates the therapeutic value of identifying and integrating platform-specific cis-acting sequences that confer increased protein synthesis on transgene expression.

These results reveal the immunosuppressive mechanism of tumorous BHLHE22 and provide a potential ICT combination therapy for patients with BHLHE22 PCa.

We sought to harness gene-modified tumor cells as a vaccine platform and developed cancer vaccines composed of breast cancer cells expressing GM-CSF (SV-BR-1-GM). Different types of cancer vaccines have been developed with moderate success, often hampered by lack of strong immunogenicity and complex manufacturing. BriaCell’s Bria OTS provides a solution by increasing vaccine immunogenicity and decreasing manufacturing costs while personalizing the therapy based on matching the patient’s HLA type.1.Lacher MD et al, Front Immunol. 2018 May 15;9:776

Anti-cancer functions of GM-CSFRα-expressing ICI were suggested. Altogether, the benefits of acquired GM-CSFRα-expressing ICI and GM-CSF for CCA treatment are proposed herein and require elucidation.

RP1 + nivo induced a deep and durable antitumor activity in pts with advanced skin cancers, including anti-PD-1 and anti-PD-1/anti-CTLA-4 failed mel. The combination was generally well tolerated, consistent with prior data. Enrollment into a registration-directed cohort of pts with anti-PD-1 failed cutaneous mel (n=125) and a cohort with anti-PD-1 failed NMSC (n=30) is ongoing.

These results show that high IL4/GMCSF levels are negatively associated with survival in EC. These relationships are independent of pathologic stage and are identified across modalities, histologic subtypes, and the presence/absence of neoadjuvant therapy.