TNFRSF17 expression

Bioinformatic analysis showed that the levels of ERβ and TNFRSF17 were elevated in lung adenocarcinoma, and were closely related to tumor stages and nodal metastasis status. These results suggested that 25-HC promoted the proliferation and metastasis of LAC by regulating ERβ/TNFRSF17 axis.

Our findings highlight the impact of sBCMA levels and its chronicity of exposure on anti-BCMA TCE and CAR T activities in MM. We further identified structural genomic events driving TNFRSF17 over-expression and their correlation to sBCMA levels facilitating tumoral immunotherapeutic escape.

In a phase I, first-in-human clinical trial (n=18; relapsed/refractory MM) combining the GSI, crenigacestat, with anti-BCMA CAR T-cell therapy (FCARH143), we recently demonstrated that plasma cell BCMA antibody-binding capacity increased a median of 12-fold among 17/18 (94%) of participants after they received a 5-day GSI "run-in" (25 mg orally administered QOD for 3 doses) [Cowan AJ, et al...Accessibility of CD38, the target of daratumumab, was significantly increased in B cells, and SLAMF7, the target of elotuzumab, was significantly increased in plasma cells... BCMA cleavage from myeloma cells' surface is a putative resistance mechanism to BCMA-targeting immunotherapy. This study assessed the single-cell transcriptome and chromatin accessibility in the bone marrow environment of 16 patients given GSI monotherapy to ultimately enhance the efficacy of subsequent anti-BCMA CAR T-cell therapy. We found that prior BCMA-targeted therapy resulted in reduced chromatin accessibility within the BCMA epigenome.

Three months after initiation of belamaf, the pt had progressive disease and teclistamab was initiated, but failed to induce another response. BCMA-directed treatment, especially CAR-T cell treatment, opens a new therapeutic era in RRMM. So far, limited data exist on mechanisms of resistance. Here, we report genetic alterations in the TNFRSF17 gene in 2 pts with underlying HR disease and early and atypical relapse after CAR-T treatment.

Genomic analysis of BMA samples from MagnetisMM-3 identified an association between higher TNFRSF17 expression in the tumor microenvironment and unfavorable outcomes, likely due to its surrogacy with increased tumor burden. Features of high-risk disease were also associated with lack of response to elranatamab. Adjusting for tumor cell content revealed additional aspects of the tumor microenvironment associated with poor response, including increased myeloid cell populations.

No abstract available

Initial real-world data of the ongoing study demonstrate the power of WGTS to add valuable information to gold standard diagnostics in 1/3 of unclear cases within 3 weeks. In the context of challenging unsolved cases, close cooperation of experts from various backgrounds (hematology, pathology, human genetics and bioinformatics) in tumor boards allows to achieve the best possible diagnoses for patients.

Furthermore, blockage of the JNK pathway by its inhibitor SP600125 resulted in significant inhibition of MM cell proliferation induced by SETD2 knockdown...Together, our data delineate that SETD2-dependent H3K36me3 modification plays a critical role in regulation cell proliferation and cell cycle by BCMA-JNK and c-Myc pathways in MM cells. Targeting the SETD2-H3K36me3 pathway represents a promising therapy for MM.

CD319 and CD269 express stably and continuously in plasma cells of MM patients at different disease stages. CD319 can be used as an alternative of CD38 for immunophenotyping and MRD detection, especially for MRD detection after DARA treatment, while CD269 is suitable for detection before BCMA-CAR-T treatment.