T-Bactum (EB23 18235Y / EB2318235Y)

Perioperative myeloid cell remodeling shapes CAR-T cell efficacy in glioblastoma.

Pedard Martin M, Castillo Cantero Luis L, Ghasemi Ali A, Marinari Eliana E et al.

Glioblastoma (GBM) is characterized by a profoundly immunosuppressive tumor microenvironment (TME) that constrains the efficacy of chimeric antigen receptor (CAR)-T cell therapy. Here, we show that surgical resection in both male mice and human GBM ex vivo induces a rapid and sustained remodeling of the TME, marked by upregulation of TREM2 in myeloid cells followed by emergence of T cell exhaustion-like phenotypes. In male mice, targeting TREM2 reshapes the perioperative TME and potentiates tumor antigen-specific CAR-T cell responses, improving intratumoral persistence, proliferation, and effector differentiation, and resulting in enhanced survival. In parallel, we identify the timing of CAR-T cell administration as a critical determinant of therapeutic outcome, with neoadjuvant outperforming adjuvant treatment by preserving CAR-T cell effector function in mice. These findings establish perioperative myeloid cell remodeling and treatment timing as key determinants of CAR-T cell efficacy in GBM.

Real-time monitoring of CAR T cell dynamics in tumor patient-derived organoids using the OrganoIDNet algorithm.

Ferreira Nathalia N, Dourlens Camille C, Scodellaro Riccardo R, Stroebel Philipp P et al.

Patient-derived organoids (PDOs) provide physiologically relevant 3D tumor models for preclinical drug testing, yet robust and automated methods to quantify dynamic responses to immunotherapies remain limited. OrganoIDNet is a deep learning-based image analysis framework that enables automated, label-free segmentation and longitudinal quantification of organoid morphology. Here, we extend the application of OrganoIDNet to evaluate chimeric antigen receptor (CAR) T cell activity against pancreatic ductal adenocarcinoma (PDAC) PDOs targeting the tumor-associated antigen CD318. CD318-directed CAR T cells were co-cultured with PDAC PDOs using a Matrigel-based sandwich system and monitored by time-lapse bright-field imaging. OrganoIDNet enabled accurate single-organoid segmentation and continuous quantification of organoid number and area across multiple effector-to-target ratios. CAR-318 T cells induced robust, antigen-dependent cytotoxicity, characterized by progressive reductions in organoid number and size and were accompanied by increased T cell activation marker expression and changes in TIM-3 expression at the endpoint. Dynamic imaging and T cell spatial analysis, further revealed close T cell-organoid interactions and early tumor cell elimination, providing time-resolved information on organoid responses and T cell proximity that complements conventional endpoint assays. By integrating organoid-immune co-cultures with OrganoIDNet-driven live-cell imaging, we established an automated longitudinal imaging assay for assessing CAR T cell-mediated responses in PDAC PDOs. The assay enabled continuous quantification of organoid number and area, together with image-based assessment of T cell proximity, across multiple effector-to-target ratios. These measurements provide time-resolved information on antigen-dependent cytotoxicity and spatial association during the observation period, supporting its potential utility as a preclinical platform for CAR T cell development and future personalized immunotherapy studies.

Mechanism and intervention strategy of thymus atrophy in cancer immunotherapy.

Zhang Haohang H, Zhang Fujie F, Li Tiantian T, Xu Sheng S et al.

Thymic atrophy is a major determinant of T-cell dysfunction and immunosenescence, as it restricts de novo T-cell generation, reduces the T-cell receptor (TCR) repertoire, hastens peripheral T-cell aging, and disrupts central immune tolerance. It presents an enormous barrier to antitumor immune surveillance as well as current cancer immunotherapies such as immune checkpoint inhibitors (ICIs) and chimeric antigen receptor T-cell (CAR-T) therapy. In this review, we discuss how age, metabolic disorders, psychological stress, cancer pathology, and cancer-directed therapies converge upon thymic epithelial cells, stromal organization, and hematopoietic progenitor trafficking leading to structural and functional thymic decline. We then describe how thymopoiesis impairment reshapes tumor immunity and therapeutic responsiveness, and summarize noninvasive imaging methods for assessment of thymic health, and highlight new strategies for thymic regeneration or functional replacement through pharmacologic agents, cytokine and endocrine modulation, mRNA-based trophic factor delivery, cell replacement, tissue engineering, and thymus-centered CAR-T platforms. Despite significant translational challenges, rapid advances in thymic regeneration biology suggest that restoration of thymic function may be a rational host-directed approach to enhance the depth, duration, and safety of cancer immunotherapy.

Residual disease in HER2-positive early breast cancer: are we escalating the RIGHT patients to T-DM1 or T-DXd?

Tjalma Wiebren W, Papadimitriou Konstantinos K