TEST:

nCounter® PanCancer Immune Profiling Panel

BRAFmutpTERTwt had higher stromal lymphocytes infiltration as compared to BRAFwtpTERTwt tumors, corroborating the transcriptomic findings. To our knowledge this is the first report of a potential link between TERT and the immune microenvironment, offering an explanation for the aggressive nature of BRAFmutpTERTmut PTC.

Furthermore, increased activity of macrophages and reduced expression of B-cells support previous studies underlining their involvement in treatment resistance. Despite limitations in sample size, these findings shed light on the mechanisms behind resistance and early relapse in cHL, which could help guide the development of targeted therapies and potentially improve early risk assessment.

Among these cases, the genes GZMA, MICB, and GNLY were significantly upregulated, suggesting their involvement in an increased immune response. The role of HPV infection status in our cases with regard to the peritumoral immune cell infiltrate remains inconclusive.

Low T cell diversity is a marker of poor overall survival at relapse. These findings suggest T cell mediated immunity is critical for chemotherapy response in DLBCL and could have implications for predicting responses to newer T cell directed therapies such as bispecific T cell and CART therapies.

Augmentation of the peritumoral immune environment in CTAhigh regions suggests a role for CTA expression in modulating tumor response. Targeted pathways to drive CTA expression may represent an opportunity to improve tumor sensitivity and response to immunotherapy in future trials.

These results suggest gene expression analysis could aid in early relapse detection and underscore the immune-modulatory role of B-cells in cHL progression.

ITGB4 was transcriptionally activated by TFAP2A, and could promote LUAD progression and inhibit CD4+/CD8+ T-cell infiltrations by activating the NF-κB signaling pathway. ITGB4 may serve as a potential immunotherapeutic target of LUAD.

TABs with TMI had a distinct transcriptome compared with normal TABs and TABs with ILA. The few genes potentially deregulated in ILA were also deregulated in TMI. Gene profiling allowed to deepen the knowledge of GCA pathogenesis.

P1; Trial completion date: May 2024 --> Dec 2024

HLA-DQ is an HLA class II molecule expressed on APCs. Patients were enrolled May 2020 to Feb 2022 and treated with standard dosing of G/nP (d1, 8, 15) and either TTX-030 40mg/kg followed by 20mg/kg every two weeks (n = 31) or TTX-030 every 2 weeks and budigalimab (anti-PD1 Ab) 500mg every 4 weeks (n = 28). TTX-030 combinations show promising clinical activity in 1L PDAC with HLA-DQhigh having marked benefit. A randomized phase 2 study (NCT06119217) is underway to further evaluate TTX-030 combination treatment based on HLA-DQ status in metastatic PDAC.

Immune patterns differed in SD-iCCA versus LD-iCCA. We identified potential biomarker candidate genes, including CRP, CEACAM6, DMBT1, and various complement factors that could be explored for augmented diagnostics and treatment decision-making.

To address the question of whether the IFNg can be analyzed using primary tumor material (P-IFNg) instead of LN-IFNg or, in the case of incongruencies, has a higher predictive value when combined with LN-IFNg, we analyzed the IFNg signature in paired samples (P and LN) from stage III melanoma pts. Paraffin primary tumor tissue from pts with stage III melanoma, treated in the OpACIN-neo, PRADO and DONIMI trials (neoadjuvant anti-PD1 +/- anti-CTLA4 +/- domatinostat), was retrospectively analyzed with the nanostring nCounter PanCancer immune profiling panel and compared to fresh frozen LN biopsies. Our results suggest that pts with concurrently high IFNg-signature expressions (high IFNg in P and LN) have a better outcome than LN-IFNg high pts only. If confirmed, these findings could inform treatment selection and prognosis.

Our findings underscore a specific immunogenetic phenotype profile in negative SLNs, emphasizing their crucial role in the initial anticancer response, immunosurveillance, and the propagation of immune tolerance from the primary cervical tumor. These results highlight the potential of SLNs as a novel target for immunotherapy strategies and underscore the importance of new imaging methods for accurately identifying SLN status without removal. Future investigations are needed to understand further the immunological interplay within SLNs and their influence on cervical cancer progression.

These findings delineate a paracrine signaling exchange between tumor cells and TAMs regulated by HUNK and dependent on IL-4/IL-4 R. This highlights the potential of HUNK as a target for reducing TNBC metastasis through modulation of the TAM population.

Purpose/Objective: The CEDAR trial was a multi-centre phase 1 clinical trial (NCT03916510) in locally advanced rectal cancer patients which combined 25x2Gy chemoradiation with concurrent capecitabine and Enadenotucirev (EnAd), a tumourselective intravenous oncolytic adenovirus. S5230 Radiobiology - Microenvironment Interpatient microbial heterogeneity is greater than dynamic microbiome shifts through treatment in this study. Certain microbiome constituents may be associated with more favourable radiation responses. The absence of significant microbial variation during treatment suggests baseline microbiome features could be further explored as a predictive biomarker.

SPINK5, a known tumor 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 in the evolution of tumors of the upper aerodigestive tract, highlighting the potential for targeting early mechanisms of disease progression.

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.