Extracorporeal photopheresis versus systemic immunosuppression for treatment of immune-related adverse events: clinical outcomes from the prospective two-arm PRIA study

Background
Immune checkpoint inhibitor-induced immune-related adverse events (irAEs) can be steroid-refractory (sr) or steroid-dependent (sd), requiring second-line therapy. Evidence guiding optimal management of sr/sd-irAEs while preserving antitumor…

Blinatumomab bypasses CD28 blockade to sustain T-cell cytotoxicity and improve survival in a xenograft B-ALL model

Background
Relapse and graft-versus-host disease (GvHD) remain primary causes of treatment failure in patients with B-cell acute lymphoblastic leukemia (B-ALL) undergoing allogeneic hematopoietic cell transplantation (allo-HCT). While abatacept (ABATA…

Tumor-derived HMGB2 induces M2-like macrophage polarization via TRIM65-mediated NLRP3 degradation to promote DLBCL progression

Background
Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin’s lymphoma. Although standard immunochemotherapy is available, 30%–40% of patients develop refractory or relapsed disease, underscoring the need to …

First-in-human, phase 1, open-label study of alomfilimab, an anti-ICOS antibody, as a single agent and in combination with anti-PD-L1 in advanced malignancies

Background
Immunosuppression mechanisms mediated by regulatory T cells (Tregs) can lead to poor clinical outcomes in patients undergoing immune-based therapies. Activation markers, such as inducible T-cell co-stimulator (ICOS), are highly expressed on…

Targeting ATF4 overcomes dual resistance to chemo-immunotherapy in gastric cancer by disrupting the DNA damage response

Background
The efficacy of chemo-immunotherapy in gastric cancer (GC) is limited by heterogeneous resistance and the lack of predictive biomarkers. However, the molecular mechanisms underlying concurrent intrinsic chemoresistance and extrinsic immunos…

USP1-mediated lipophagy-lipogenesis axis drives cholangiocarcinoma progression and immune evasion

Background
Cholangiocarcinoma (CCA), a malignancy arising from biliary epithelial cells, features a tumor microenvironment (TME) characterized by metabolic dysregulation and immunosuppression. Although diverse metabolic aberrations have been observed,…

VSIG4 suppresses antitumor T cell immunity via the SLC3A2-dependent metabolic-ionic checkpoint

Background
Immune checkpoint blockade therapy aims to restore T-cell function within the tumor microenvironment (TME), eliciting durable antitumor responses. However, clinical response rates to PD-1/PD-L1 inhibitors remain limited, particularly in imm…

From viral drift to tumor drift: why cancer immunotherapy needs B cells and dynamic adaptation

Current T-cell-based immunotherapies—chimeric antigen receptor T (CAR-T) cells, checkpoint inhibitors, and neoantigen vaccines—share a fundamental vulnerability: they target fixed antigens while tumors continuously evolve. Like influenza v…

CD19/CD22 bivalent CAR T cells in children, adolescents and young adults with B-ALL: final phase 1 trial results

Multiantigen targeting chimeric antigen receptor (CAR) T cells have emerged as a strategy to mitigate antigen escape observed after single antigen targeting therapy. Our initial experience with a bivalent CD19.22.BB CAR T-cell construct in children, a…

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