TEST:

nCounter® PanCancer IO 360™ Panel

We show that exercise training during NAC, which improves cardiorespiratory fitness, is associated with increased frequencies of TILs and maturity of TLS. These data suggest that exercise during NAC enhances the immune system possibly to be suitable for immunotherapy.

Methods Gene profiling analysis was performed using NanoString IO360 panel from PBMCs of pts with cutaneous melanoma treated with antiPD1 (pembrolizumab or nivolumab) in both clinical setting (adjuvant and first line therapy). Conclusions In this retrospective study, we identify gene signatures model associated with the onset of skin toxicities related to anti-PD1 treatment in stage III/IV unresectable and resected stage III melanoma pts. Further investigations are needed in order to validate the signature in an independent dataset.

In conclusion, we observed a convergence of both mutational and expression signatures on angiogenesis signaling pathways in our AS-B cases. The spatial transciptomic data revealed that AS-B was enriched for tumor-infiltrating macrophages and T-cells which might have implications on the role of immunotherapy.

We characterized the expression of CLDN6 across the different cohorts of OSCC samples and further investigated the relationship within the tumor immune microenvironment coupled to genes related to the prognosis of OSCC. A better understanding of the TME and gene expression profiling of OSCC tumors and the effect of smoking will allow us to tailor the treatment of patients to continue to improve outcomes.

Significant cytotoxicity was observed in 2 out of 10 patient tumors (20%) as a monotherapy and 4 out of 10 (40%) when used in combination with atezolizumab. These data support the prospects of NXI-101 as a first-in-class therapeutic for the treatment of NSCLC when used alone or in combination with an immune checkpoint inhibitor. Moreover, the findings highlight the PDOTS platform's substantial value in capturing patient-specific tumor response variability and providing robust support for the mechanistic evaluation of cancer therapeutics.

Lastly, IDO1 and PDL1-specific CD4+ T cell clones from melanoma patients treated with IO102-IO103 vaccine could selectively target cells differentially expressing IDO1 or PDL1.Our data collectively show that cells expressing IDO1 and PD-L1 represent distinct populations in the TME thus targetable by the IDO1-PD-L1 vaccination approach...These data are supported by ex vivo functional assays using target specific T cells from vaccinated patients. Altogether, our data support the use of a dual antigen approach to reduce the immunosuppression and enhance anti-tumor effect.

At baseline, most patients exhibited low CD8+ TIL, PD-L1 and TIS, with enhanced immune activation following treatment in the TME and blood including increased immune-related gene expression, CD8+ TIL, peritumoral CD8+ T cells and TIS. Four of 5 pts with negative predictive baseline biomarkers [CD8+TIL/PD-L1/TIS]low experienced pCRs supporting activity of IL12/anti-PD1 based regimens in this setting.

GeoMx WTA panel provided an unbiased view of 18,000 protein-coding genes at specific TME regions. These counts were successfully mapped to the 12 ROIs on the tissue. A pseudo-TIS score was generated using the same 18 gene signature from the WTA panel for each ROI.

IL20RA and SOX10 represent potential biomarkers for TNBC risk that may serve as a stratification tool for NHB women. The results of this study have the potential to improve assessment and management of TNBC risk among NHB women, thereby contributing significantly to reducing health disparities in breast cancer outcomes.

Furthermore, the differences between the EAOC subtypes suggest distinct processes driving EC or CCC development from endometriotic lesions, with a more inflammatory signature in EC that may be promising for the development future therapeutic strategies. This study sheds light on immune dynamics in ovarian endometriosis and EAOC, offering potential avenues for future research.

Validation using immunohistochemistry further supported these findings. In conclusion, the findings highlight the significance of using matched-paired samples to identify cancer lineage-specific therapies that may improve brain metastasis patients outcomes.

Our data offer a cellular and molecular insight into a case of clinical pseudoprogression observed during tolinapant treatment. Understanding pseudoprogression is important for clinical investigators and patients to ensure treatment with tolinapant, or other IAP antagonists, are not discontinued prematurely.

Two cohorts of FLT3-mut AML patients treated either with Midostaurin in combination with intensive chemotherapy (M cohort) as induction or Gilteritinib (G cohort) as salvage at Seràgnoli Hematology Institute of Bologna were enrolled. Conclusions. This study portrays evolutionary trajectories under FLT3i-containing regimens pressure and highlights novel preliminary differences in immune transcriptomic profile associated with FLT3i effectiveness.

The TIS (tumor inflammation signature) and IFN-γ signatures constitute predictive biomarkers to identify patients with NSCLC patients who would possibly benefit from ICI therapies.

Patients were lymphodepleted with fludarabine and cyclophosphamide...Multi-modal analyses of WU-NK-101 highlight unique transcriptional and functional states, which could underpin in vivo potency and persistence. WU-NK-101 are currently being evaluated in a phase 1 study of R/R AML (#NCT05470140).

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.

Moreover, we acquired an additional dataset of pre-treatment immune-related gene expression profiling obtained from the BM of 30 flotetuzumab-treated (CD3 x CD123 bispecific antibody) refractory/relapsed (R/R) adult AML patients (NCT02152956; Vadakekolathu et al., 2020) for TIDE-based immune deconvolution (Jiang et al., 2018)...Lastly, for the first time, we identified TLS-like aggregates in the BM of AML patients, which have been associated with immunotherapy response in many cancers (Schumacher & Thommen, 2022). Additional studies to further characterize the function and relevance of these lymphoid aggregates are ongoing.

This study confirmed evolutionary trajectories often involving RAS pathway mutations as an intrinsic mechanism of resistance to Gilteritinib therapy. Of note, differences in immune transcriptomic profiles, involving mainly CD8+ T-Cells and NK-Cells, were associated with response, pointing to a previously unappreciated role of the immune system in mediating response to Gilteritinib.

ALC above 1.01 × 10/L and absence of liver metastases were significantly associated with DCB in ICI-treated patients with NSCLC. GEP was only feasible in 20% of the patients. GEP-derived signatures may be associated with clinical outcomes, and PD-L1 could be assessed by GEP rather than IHC.

"Conclusions Antigenic Emm55-derived peptides provoke individual immune responses via an antigen/interferon-dependent process in those patients with the longest survival after subsequent anti-PD1 treatment. Subsequent studies are being planned for the clinic."

Conclusions In this retrospective study, we found a gene signature model able to predict the onset of toxicities (arthralgia and fever) related to anti-PD1 treatment. Further investigations are needed to get additional information.

RNA and protein analyses demonstrated changes in the TME including cGAS-STING activation and immune cell infiltration in BRCA1/2m tumors, consistent with preclinical models. Deep phenotyping of tumor and immune cells, along with spatial analysis, provided valuable insights into the distinct responses, such as the presence of CD68+ macrophage populations associated with longer PFS, potentially contributing to a more immunostimulatory TME favorable for T cells.

Conclusions This integrated automated AI-driven high-throughput workflow for selection of ROIs to deeply characterize the whole transcriptome and 500 immuno-oncology-related proteins in tumor epithelium and stromal compartments of the TME. These findings provide an objective method to automatically select tissue regions for high-plex spatial-omic analysis, supporting discoveries that may improve the understanding of the underlying mechanism of TNBC tumor progression, potentially discover new combinations for drug targets and novel biomarkers that are easily translatable to large study cohorts.

Conclusions These results demonstrate the reliability of these methods at Cerba Research giving confidence to clients for use in clinical studies. Cerba Research is committed to expand these validations to maximize a bulk and spatial Omics offering.

This could explain the prognostic role of NLR. Further investigations are needed to get additional information.

This preliminary report unveils the importance of assessing immune leukocyte cellular fractions and pathways for future prognostic biomarker discoveries in mucoepidermoid carcinoma as per the involvement of CD45-driven inflammatory and immune mediators in high grade mucoepidermoid carcinoma in non-responders to treatment. These findings will potentially contribute to the development of novel personalised immunotherapies.

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

Collectively, these data establish a new function for the actin cytoskeleton regulator hMENA in modulating cancer cell intrinsic type I IFN signaling and extrinsic mechanisms that promote protumoral macrophages and favor EMT. These data highlight the role of actin cytoskeleton disturbance in activating immune suppressive pathways that may be involved in resistance to ICB in NSCLC.

"This could explain the prognostic role of NLR. Further investigations are needed to get additional information."

Conclusions Our data confirm the relevance of immunological exhaustion in lymphatic tissues of NSCLC patients. Increased IDO1 expression is associated with higher ECOG score and worse survival and needs to be further investigated.

Conclusions AXA-042 demonstrates on-target biological activity in patient blood samples. Further biomarker analyses are ongoing and will be correlated with clinical activity in a larger number of patients.

TIDE scores in tumor and regional lymph nodes may indicate a dysfunctional immune status and can predict postoperative survival in NSCLC.

LUAD and their brain metastasis express high levels of VISTA. The results urge the development of lineage-tailored therapeutic approaches to successfully prevent or treat brain metastases.

Moreover, their predictive power increase when they are analysed as a signature, being postulated as biomarkers for selecting the best therapeutic choice. However, further validations in a prospective cohort are warranted to elucidate the clinical potential of this signature.

Interestingly, none significantly differentially expressed genes were observed when comparing rSTUMP with LMS and nrSTUMP with LM.ConclusionThe here presented data demonstrates the heterogeneity of the immune-related transcriptomic landscape of uterine STUMP based on their clinical behavior. Specifically, nrSTUMP and rSTUMP have been shown to harbor molecular profiles closer to LM and LMS, respectively.These differences could be exploited to pinpoint novel diagnostic/prognostic markers and correctly stratify STUMP according to their malignant potential.

To date, the ICI cemiplimab and pembrolizumab remain the only systemic therapies approved for cSCC not amenable for curative surgery or radiotherapy. Digital spatial profiling of responders highlighted the relevance of the tumour immune microenvironment and its utility in prognosis. ConclusionIn conclusion, this work provides a first indication for potential biomarkers and factors that govern the response to immune checkpoint inhibition in cSCC.

P=N/A; This multiomics approach was able to identify immune cell subsets and expression levels of genes associated to PFS in patients with PD-L1 <50% NSCLC treated with first-line pembrolizumab. These preliminary data will be confirmed in the larger multicentric international I3LUNG trial (NCT05537922).

Integrative molecular analysis of the tumor microenvironment of GAC identifies an Inflamed class of tumors that complements previously proposed tumor-based molecular clusters (CIN, MSI, EBV, GS). Such findings may provide the rationale for exploring novel immunotherapeutic approaches for biomarker-enriched populations in order to improve GAC patient's survival by means of a paradigm shift in precision immune-oncology.

The research was funded by: NCCS Cancer Fund (Research) (NCCSCF-R-YR2021-JUN-SSD1), Tanoto Foundation Professorship in Medical Oncology, New Century Foundation Limited, Ling Foundation, Singapore Ministry of Health’s National Medical Research Council Research Transition Awards (TA21jun-0005 and TA20nov-0020), Large Collaborative Grant (OFLCG18May-0028), and Collaborative centre grant (TETRAD II)... Our AITL-PI identified 3 different subgroups of patients with disparate outcomes based on their presenting clinical parameters. Low risk patients had 5-year OS exceeding 80%. Gene expression profiling found unique immune and oncogenic signalling profiles in the low risk group that would allow for further dissection in future molecular analyses.

This pilot study identified trends in gene expression associated with clinical outcomes. While statistical significance was precluded by limited sample size, our results suggest trends toward increased TME immune cell infiltration in age 6 month OS. Rational drug development for affected patients should target these specific abnormalities.

We selected 58 mUC pts who received at least 2 cycles of ICI (atezolizumab or pembrolizumab) between 2015-2020 and had pre-Tx archival formalin fixed paraffin-embedded (FFPE) tissues available. In our cohort of mUC pts treated with ICI, we found an association between signatures of tumor immunogenicity (APM and Immunoproteosome) and anti-tumor immune activity (IFN Gamma, IFN Downstream, TIS) in pre-Tx tissue with favorable response to therapy (including SD). These findings are hypothesis generating and need to be further validated in prospective trials. Ongoing genomic and immunologic correlative studies in our cohort will further help understand comprehensive biomarkers of response and resistance to ICI in pts with mUC.

Background: Biomarker driven therapies are increasingly being used for gynecologic cancers, with mirvetuximab soravtansine, a Folate Receptor alpha (FRa) targeting antibody drug conjugate (ADC) being a recent FDA approved agent for patients with FRa positive PROC... Based on this analysis of a limited sample size, there does not appear to be an association between FRa and NaPi2b expression, with the majority of NaPi2b positive samples not being FRa positive. Additionally, general NaPi2b prevalence and the correlation of expression between RNA and IHC suggest that NaPi2b may be a rational biomarker to integrate in RNA tumor panel testing. This research underscores the importance of early, comprehensive testing of all relevant biomarkers to guide therapy selection, and suggests that additional research is needed to evaluate the potential association between FRa and NaPi2b expression via IHC.