TEST:

nCounter® PanCancer Immune Profiling Panel

No abstracts available

" Tissue and longitudinal blood specimens from phase III trial S1400I in metastatic lung squamous cell carcinoma (SqNSCLC) patients treated with nivolumab monotherapy (nivo) or nivolumab plus ipilimumab (nivo+ipi) were subjected to multi-omics analyses including multiplex immunofluorescence (mIF), nCounter PanCancer Immune Profiling Panel, whole-exome sequencing, and Olink. The frequency, distribution and clustering of immune cells relative to malignant ones can impact ICI efficacy in SqNSCLC patients. High CNV burden may contribute to the cold immune microenvironment. Soluble inflammation/immune-related proteins in the blood have the potential to monitor therapeutic benefit from ICI treatment in SqNSCLC patients."

The Neo ComprehensiveTM Solid Tumor pan cancer assay enabled simultaneously analysis of both DNA and RNA in one integrated workflow with an accompanying DragenTM bioinformatics analysis platform and provided comprehensive genomic profiling of sequence and structural variants, as well as genomic signatures such as TMB and MSI in OSCC patients. Utility of the NanoString PCIP highlighted immune-relevant gene expression changes within the different sample cohorts. The detailed molecular information highlighted by our study emphasizes the need for improved patient classification based on smoking status in the management of OSCC and also in establishing potential therapeutic options based on the many altered cell signaling pathways that we identified.

There are significantly fewer cytotoxic and dendritic cells in late-stage MSI-H CRC, compared to early-stage MSI-H CRC, which is associated with decrease expression in JAK-STAT-IFN-γ- and antigen processing-related pathways.

High CTA and type-I IFN expression in resected SBNET identifies patients with longer survival, agnostic of stage or grade. While CTA expression has been implicated in tumor immunogenicity, this is the first work to identify a clinically relevant signal in SBNET. Increased IFN in CTA-high tumors, corroborated by increased stromal NK cell activation, suggests that enhanced immunogenicity may drive this survival difference.

SPINK5, a known tumour suppressor gene in HNSCC, was already downregulated in low-grade dysplastic lesions, indicating an early deactivation in the evolution of the disease. Genomic alterations as well as aberrant immune gene expression can be observed early on in the evolution of tumours of the upper aerodigestive tract, highlighting the potential for targeting early mechanisms of disease progression.

P1; Trial completion date: Jan 2023 --> May 2024

The frequency, distribution and clustering of immune cells relative to malignant ones can impact ICI efficacy in SqNSCLC patients. High CNV burden may contribute to the cold immune microenvironment. Soluble inflammation/immune-related proteins in the blood have the potential to monitor therapeutic benefit from ICI treatment in SqNSCLC patients.

"High expression of CTA and type-I IFN in resected SBNET is associated with longer survival, agnostic of stage or grade. While CTA expression has been implicated in tumor immunogenicity, this is the first work to identify a clinical signal in SBNET. Increased IFN in CTA-high tumors, corroborated by increased stromal NK cell activation, suggests an immune-mediated component of improved survival."

In DMF-treated patients, we observed a strong immunomodulatory effect after treatment: A subversion of exhausted CD8 T cells, NK CD56dim cells, Tregs, neutrophils, CD45+ cells, T cells, B cells, and macrophages was reported between the two analyzed time-points, as well as the reduction in pro-inflammatory pathways and molecules, including cytotoxicity, pathogen defense, antigen processing, adhesion, cell cycle, chemokines, cytokines, and interleukins. The inflammatory psoriatic microenvironment can be modulated using DMF with encouraging results, achieving an immune-tolerant and non-inflammatory condition through the regulation of both innate and adaptive immunity.

In fact, Natalizumab (anti-CD49d mAb) is administered in multiple sclerosis to impede entrance and accumulation of B cells in the brain...Herein, we have demonstrated that DLBCL cells at diagnosis already own specific transcriptomic and (epi)genetic hallmarks that could confer a higher capacity to infiltrate the CNS. Validation of these findings in larger cohorts of patients could improve selection of patients with an increased risk of CNS involvement in need of prophylactic CNS-directed therapies at diagnosis.

GEP analysis showed upregulated expression of genes related to T-cell functions, cytotoxicity functions, cytotoxic cells, or TH1 cells which are more pronounced in pts with PR/CR. Conclusions Significant early and sustained increases of circulating biomarkers and ALC substantiate the systemic stimulation via the APC activator efti and show that repeated minimally-invasive liquid biopsies, i. e. , blood samplings, are key in detecting this systemic stimulation.

P2; Recruiting --> Completed | Trial completion date: Mar 2023 --> Jul 2023

Paquinimod (PaQ) and Tasquinimod (TasQ) were administered at a dosage of 25 mg/Kg in drinking water ad libitum for 4 weeks... Genetic and pharmacological targeting of S100-A9 impairs CLL cell growth in vivo, probably through a MAPK pathway-dependent mechanism. This data demonstrates for the first time the significance of targeting S100-A9 as a novel therapeutic approach in CLL.

These results suggest that normothermic ex-vivo liver perfusion of livers prior to transplant reduces expression of genes involved in IRI, which may contribute to improved outcomes.

BP-irAE exhibited activation of the TLR4/complement-driven classical innate immune response pathway, with dermal T 1 immune cell polarization and decreased Tregs in the blister floor. TLR/complement signaling may underlie the immunopathogenesis of BP-irAE.

"Even if preliminary, these data indicate that gene expression analysis helps in the early identification of relapsing iPET- cHLs and that progression in this disease is restrained by an immune-protective microenvironment of which B-cells are crucial component."

"The research was funded by: Servier Laboratoires Introduction: The Nordic Lymphoma Group (NLG) performed a dose-finding/expansion trial evaluating pixantrone, etoposide, bendamustine and, in CD20+ lymphomas, rituximab (P[R]EBEN) in patients (pts) with relapsed diffuse large B-cell (DLBCL) or peripheral T-cell (PTCL) lymphomas. The P[R]EBEN regimen is feasible on an out-pt basis and shows encouraging response rates and DoR. In PTCL, we observed an overrepresentation of AML/MDS, possibly related to the use of etoposide in multiple treatment lines. Gene expression analysis identified signatures and single genes predictive of long-term response."

"Key differences in the TME are evident in DLBCL across treatment timepoints with reduced T cell infiltration and function at relapse demonstrated by immune gene expression and spatial transcriptome analysis. These findings have implications for clinical practice as they may explain poor response to immune checkpoint therapy at relapse and could have implications for predicting responses to newer T cell directed therapies such as bispecific T cell and CAR T therapies."

Results show a higher chemokine, adhesion and proliferation signaling in DLBCL patients that will relapse in the CNS. Of notice, BTLA, CCR6 and IL7R proteins have been previously reported to be implicated in B cell CNS entrance in B-cell malignancies. Also, the ITGA4 gene codifies for the integrin α4 subunit (CD49d) of the Very Late Antigen-4, which is required for B cell migration across the BBB.

We identified a feasible transcriptomic signature with a promising signal of ICI efficacy prediction in the so far disappointing immune biomarkers field. In a near future, predict ICI efficacy will be a major challenge with three pivotal questions. When, balanced with the new data on ICI use in early-stage lung cancer or widely pretreated patients.

High expression of CTA and IL signatures in resected SBNETs identified patients with improved survival agnostic of stage. While CTA expression across multiple tumor subtypes have been implicated in their immunogenicity and potential for therapeutic targeting, this is the first work to identify a clinically relevant signal in SBNET. The concurrent increase of key cytokines (which are known to mediate anti-tumor activity) among CTA-high patients suggests an immune-mediated component to their improved survival.

Enhanced labeling by Granzyme-B was observed within and adjacent to the pHIFU treated area, but not in the non-treated tumor tissue; no difference in CD8 + staining was observed between the treatment groups. Gene expression analysis showed that the pHIFU + gem combination treatment lead to significant downregulation of 162 genes related to immunosuppression, tumorigenesis, and chemoresistance vs gem only treatment.

We preliminary identified CXCL1 and CXCL6 as candidate genes that might have the potential to serve as therapeutically relevant biomarkers in HCC patients. This might pave the way to improve patient selection for TACE in HCC patients beyond expert consensus.

A set of genes were deregulated in TABs both with TMI and ILA versus normal TABs, indicating that ILA might represent the early stages of the disease. Gene profiling allowed to deepen the knowledge on GCA pathogenesis.

In the LOKON002 phase I/II clinical trial (NCT03225989), therapy with LOAd703 (delolimogene mupadenorepvec) is investigated in combination with gemcitabine-based chemotherapy in patients with advanced cancer. In conclusion, LOAd703 therapy in combination with chemotherapy generated an inflamed tumor microenvironment in tumors that are normally seen as immunologically “cold”. Hence, LOAd703 may be able to prime tumors for immune checkpoint inhibitors or other immunotherapies, such as adoptive T or NK cell transfer.

Our data, showing an increase of M2 macrophage in TME of ESCC compared with its precancerous esophageal dysplasia, suggest that evolution of immune TME may play a role in the progression of esophageal dysplasia to ESCC. (Funded by MOST 108-2314-B-002-076-MY3, MOST 109-2314-B-002-231-, MOHW 111-TDU-B-221-114006, NTUCCS-110-10, and NTUCCS-111-05)

TPST-1120 was well tolerated and showed signs of activity in a phase I trial as monotherapy and in combination with nivolumab (NCT03829436). TPST-1120 treated patients with PR demonstrated fatty acid oxidation perturbations and immune gene expression changes as potential biomarkers of clinical benefit. Increased frequencies of responding patients bearing PI3K pathway or IDH mutations may reveal populations likely to benefit from treatment with TPST-1120. 1.

These results highlight the low or absence of mRNA levels of the canonic targetable ICs in medulloblastomas. Importantly, the analysis revealed overexpression of CD24 and CD276, which can constitute prognostic biomarkers and attractive immunotherapy targets for medulloblastomas.

Patients with longer overall survival had a higher proportion of CD8+ T cells, CD4+ T memory cells, NK cells and, unexpectedly, T regulatory cells. Using a transcriptomics platform with certain advantages for deployment in a clinical setting, our multi-cancer meta-analysis of immune gene expression and overall survival data has identified a specific transcriptional profile associated with poor overall survival.

High expression of CTA and IL in resected SBNETs correlates with improved survival agnostic of stage. While CTA expression across multiple tumor subtypes have been implicated in their immunogenicity and potential for therapeutic targeting, this is the first work to identify a clinically relevant signal in SBNET. The concurrent increase of key cytokines (which are known to mediate anti-tumor activity) among CTA-high patients suggests an immune-mediated component to their improved survival.

For paquinimod (PaQ) treatment we transferred 15x10^6 Eu-TCL1 splenocytes into C57BL/6 mice... S100A9 inhibition not only impairs CLL growth in vivo, it also decreased the CLL-induced immune dysfunction, probably through a MAPK pathway dependent mechanism. The data demonstrates for the first time the significance of S100A9 targeting in CLL as a novel immunotherapeutic approach.

The patients were treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP)-like immunochemotherapy, and the findings correlated with patient demographics and survival. The TME of GCB and ABC-like DLBCL are distinct by composition, cell-cell interaction patterns and in terms of prognostic biomarkers.

Complement activation in the TME was significantly associated with poor OS and was correlated with TAM M2 in patients with de novo metastatic BRAF V600E mutant CRC.

Trial Registration TPST-1120 as Monotherapy and in Combination With Nivolumab in Subjects With Advanced Cancers (NCT03829436). Patients with PR demonstrated gene expression changes that implicate immune activation and alleviation of immune suppression as potential biomarkers of clinical benefit. Increased frequencies of responding patients bearing PI3K pathway or IDH mutations may reveal populations likely to benefit from treatment with TPST-1120.

PDC and AC possess specific and different expression profiles of immunoregulatory genes even in the presence of a similar histological pattern of progression. Unexpectedly, progression of PC to AC is not associated with a wide deregulation of immunoregulatory mechanisms. However, a subset of genes is consistently impaired during AC progression, whose role as biomarkers and functional mechanisms need to be assessed and validated in future studies.

We performed immunohistochemistry in a total of 119 cases (54 SLNs of patients with recurrence and matched 65 SLNs of those without recurrence) and found CD2 and ATF2 were significantly decreased in SLNs of EBC patients with recurrence. Conclusions The Pattern of immune gene expression of SLNs, especially C2 and ATF2 could be an additional prognostic marker for predicting recurrences of EBC.

Conclusions L+E may have the ability to adjust the TME. A pre-treatment immune-suppressive TME was associated with worse clinical efficacy, but pts with a transformed immune-active post-treatment TME after L + E were associated with better outcome.

To our knowledge, this study is the first to show down-regulation of CTLA4 in clinical cervical cancer tissues after treatment with radiotherapy.

Our findings demonstrate that α-SMA-positive CAFs might enhance tumor growth via secretion of OPN.

Pts with a high IFN-y score in pre-treatment biopsies are more likely to respond to neoadjuvant IPI + NIVO with favorable EFS. A rapid gene expression analysis enables the IFN-y score to be used in daily clinical practice to identify pts who might qualify for treatment escalation or de-escalation. The DONIMI study [NCT04133948] currently investigates different neoadjuvant treatment combinations in stage III melanoma pts based on their intratumoral IFN-y score.

SCC samples from 82 eligible patients treated with combined nivolumab+ipilimumab (N+I) or single agent nivolumab (N) were subjected to multiplex immunofluorescence (mIF, n = 82) and NanoString (ncounter PanCancer Immune Profiling Panel, n = 32). Our findings suggest a potential advantage in PFS and OS with an increased presence of cytotoxic immune cells and genes associated with the recruitment and proliferation of these cell types before therapy.