Anti-metabolite chemotherapy increases LAG-3 expressing tumor-infiltrating lymphocytes which can be targeted by combination immune checkpoint blockade

Background
Antibodies that target immune checkpoints such as cytotoxic T lymphocyte antigen 4 (CTLA-4), programmed cell death protein/ligand 1 (PD-1/PD-L1) are approved for treatment of multiple cancer types. Chemotherapy is often administered with im…

Phase II basket trial of dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors (DART) SWOG S1609: the desmoid tumors

Background
Dual inhibition using anti-programmed death-1 (PD-1) and anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) checkpoint inhibitors has proven effective in many cancers. However, its efficacy in rare solid cancers remains unclear. Desmoid tumors …

Targeting epigenetic regulation and post-translational modification with 5-Aza-2 deoxycytidine and SUMO E1 inhibition augments T-cell receptor therapy

Background
Cellular immunotherapy using modified T cells offers new avenues for cancer treatment. T-cell receptor (TCR) engineering of CD8 T cells enables these cells to recognize tumor-associated antigens and tumor-specific neoantigens. Improving TCR…

Metabolic reprogramming of hypoxic tumor-associated macrophages through CSF-1R targeting favors treatment efficiency in colorectal cancers

Background
Tumor-associated macrophages participate in the complex network of support that favors tumor growth. Among the various strategies that have been developed to target these cells, the blockade of the colony-stimulating factor 1 receptor (CSF-…

Neurofilament light chain levels as an early predictive biomarker of neurotoxicity after CAR T-cell therapy

Immune effector cell-associated neurotoxicity syndrome (ICANS) remains a significant cause of morbidity associated with CD19-targeted chimeric antigen receptor (CAR) T-cell therapy. Early prediction of patients who will develop ICANS would be crucial …

BCMA-BBZ-OX40 CAR-T Therapy Using an Instant Manufacturing Platform in Multiple Myeloma

Background
Chimeric antigen receptor (CAR)-T cell has revolutionary efficacy against relapsed/refractory multiple myeloma (R/R MM). However, current CAR-T cell therapy has several limitations including long vein-to-vein time and limited viability.

Me…

MTA-cooperative PRMT5 inhibitors enhance T cell-mediated antitumor activity in MTAP-loss tumors

Background
Hyperactivated protein arginine methyltransferases (PRMTs) are implicated in human cancers. Inhibiting tumor intrinsic PRMT5 was reported to potentiate antitumor immune responses, highlighting the possibility of combining PRMT5 inhibitors (…

Spatial colocalization and combined survival benefit of natural killer and CD8 T cells despite profound MHC class I loss in non-small cell lung cancer

Background
Major histocompatibility complex class I (MHC-I) loss is frequent in non-small cell lung cancer (NSCLC) rendering tumor cells resistant to T cell lysis. NK cells kill MHC-I-deficient tumor cells, and although previous work indicated their p…

Circumventing resistance within the Ewing sarcoma microenvironment by combinatorial innate immunotherapy

Background
Pediatric patients with recurrent/metastatic Ewing sarcoma (ES) have a dismal 5-year survival. Novel therapeutic approaches are desperately needed. Natural killer (NK) cell number and function are low in ES patient tumors, in large part due…

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