TEST:

nCounter® PanCancer IO 360™ Panel

This study highlights transcriptional signatures associated with breast cancer CNS metastases, emphasizing the role of immune modulation in metastatic progression. The identified genes have potential as prognostic biomarkers and therapeutic targets, supporting the need for site-specific molecular profiling in metastatic breast cancer management.

We present here a detailed, treatment-oriented molecular comparison between two histologically distinct endometrial cancer subtypes, UPSC and UCS. Assessment of unrepaired DNA damage and, by proxy, DNA repair capacity, gives context to the immune transcriptomic landscape. Our data suggests that the immune exhausted molecular landscape of UPSC may be more amenable to IO than that of UCS, while the DNA repair-robust UCS may be more vulnerable to agents targeting DNA Damage repair such as PARP inhibitors. Further, our data suggests that estimation of DNA repair capacity via RADD may be as treatment informative as molecular sequencing.

Whole-blood gene-expression profiling enables early identification of patients at high risk for irAEs during anti-PD-1 therapy. These predictive biomarkers may guide personalized toxicity monitoring in melanoma treatment.

Our findings reveal novel fusions and validate altered replication pathways related to HPV42 in DPAC.

P1/2, N=18, Recruiting, Universitair Ziekenhuis Brussel | Phase classification: P1 --> P1/2 | Trial completion date: Dec 2020 --> Dec 2025 | Trial primary completion date: Dec 2020 --> Dec 2025 | Completed --> Recruiting

Combination therapy with poly-ICLC, especially through IT route, and anti-PD-1 provides significantly greater antitumor effects than anti-PD-1 monotherapy in syngeneic mouse models of HCC.

Conclusions Overall, these preliminary data reveal a potential crosstalk between deregulated cancer cell proliferation and MARCO+Mφs in mediating disease progression and ICI resistance of ccRCC. Mechanistic experiments will be performed to confirm this assumption and to test whether targeting cancer cell-deregulated proliferation (e.g. by FDA-approved CDK4/6-TAs) could reshape ccRCC-mediated Mφ polarization and improve ICI efficacy.

Conclusions : These findings underscore the significance of pre-treatment systemic inflammation (e.g. serum TNFa levels), product T cell phenotype, TMTV, CAR T-cell expansion, tumor IFN signaling and FLIPI as independent factors associated with clinical outcomes in patients with r/r FL treated with axi-cel. These results offer insights into mechanisms of resistance and toxicity, risk stratification, combination therapy and development of next-generation CAR-T therapy for patients with r/r FL.

We then profiled a wet-lab cohort of 37 FLT3-mut AML patients treated either with Midostaurin plus chemotherapy (M) or Gilteritinib (G) at Bologna Hematology Institute by using the PanCancer IO 360 Panel (NanoString Technologies, San Diego, CA). S.R. & A.C. equally contributed

Methods Pre/perimenopausal pts with no prior systemic therapy for aggressive HR+/HER2− ABC were randomized 1:1 to RIB + letrozole/anastrozole + goserelin or physician's choice of combo CT. Contrary results in the CT arm suggest that these signatures warrant further studies on their potential predictive value. These data are hypothesis generating and should be interpreted with caution due to small sample sizes.

These effects may play a substantial role in delaying progression in end-stage patients. Additional work is ongoing to demonstrate this new mechanism of action across clinical settings and patient populations.

P1/2 | "Background TOPACIO was a phase I/II study evaluating the PARP inhibitor (PARPi) niraparib in combination with the anti-PD-1 antibody pembrolizumab in patients with locally advanced or metastatic triple-negative breast cancer (TNBC, n=55), irrespective of BRCA mutation status. The study protocol and/or other relevant documents received central approval by the Dana-Farber institutional review board and/or relevant competent authorities at each site. All patients supplied written informed consent for their participation in the study."