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Cross-priming in cancer immunology and immunotherapy.
Nat Rev Cancer
January 2025
Program of Immunology and Immunotherapy, Cima Universidad de Navarra, Pamplona, Spain.
Cytotoxic T cell immune responses against cancer crucially depend on the ability of a subtype of professional antigen-presenting cells termed conventional type 1 dendritic cells (cDC1s) to cross-present antigens. Cross-presentation comprises redirection of exogenous antigens taken from other cells to the major histocompatibility complex class I antigen-presenting machinery. In addition, once activated and having sensed viral moieties or T helper cell cooperation via CD40-CD40L interactions, cDC1s provide key co-stimulatory ligands and cytokines to mount and sustain CD8 T cell immune responses.
View Article and Find Full Text PDFImpact of statin therapy on CD40:CD40L signaling: mechanistic insights and therapeutic opportunities.
Pharmacol Rep
February 2025
Center for Global Health Research, Saveetha Medical College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India.
Statins are widely utilized to reduce cholesterol levels, particularly in cardiovascular diseases. They interface with cholesterol synthesis by inhibiting the 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductase enzyme. Besides their primary effect, statins demonstrate anti-inflammatory and immune-modulating properties in various diseases, highlighting the pleiotropic effect of these drugs.
View Article and Find Full Text PDFBone marrow stromal cells protect myeloma cells from ferroptosis through GPX4 deSUMOylation.
Cancer Lett
December 2024
Shandong Provincial Key Laboratory of Precision Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, China. Electronic address:
Bone marrow stromal cells (BMSCs) are vital for preventing chemotherapy induced apoptosis of multiple myeloma (MM), but roles and machinery in other forms of cell death have not been well elucidated. Here, using an in vitro BMSC-MM interacting model, we observed BMSCs protected MM cells from labile iron pool (LIP) and reactive oxygen species (ROS) triggered ferroptosis by elevating glutathione peroxidase 4 (GPX4). Mechanistically, direct interaction with BMSCs upregulated the expression of SUMO-specific protease 3 (SENP3) in MM cells through CD40/CD40L signaling pathway, and SENP3 de-conjugated SUMO2 at lysine 75 residue to stabilize GPX4 protein, thereby consuming ROS to obviate ferroptosis in MM cells from the Vk∗MYC mouse model, as well as in CD138B220 cells separated from the Cd40l;Prx1 mice (CD40-CKO) and Sumo2 knock out (SUMO2-KO) mice.
View Article and Find Full Text PDFMessages in CD40L are encrypted for residue-specific functions.
Cytokine
January 2025
JSPS Government Homeopathic Medical College, Hyderabad 500013, India. Electronic address:
CD40-CD40-ligand (CD40L) interaction plays crucial immunoregulatory roles, as CD40 signals through different signaling intermediates to convert the messages from CD40L to effector functions. Being a TNFα receptor family member, CD40 binds TNFα receptor-associated factors, assembles signalosome complexes and decrypts the messages from CD40L through different signaling modules to result in residue-specific effector functions. The evidence for such a residue-specific message encryption first came from the CD40L mutations resulting in X-linked hyper-IgM syndrome, as the extent of effects varied with the residue mutated.
View Article and Find Full Text PDFHuman B-cells can form Hetero-aggregates with Blood Platelets: A Novel Insight into Adaptive Immunity Regulation in Multiple Sclerosis.
J Mol Biol
January 2025
University of Lodz, Faculty of Biology and Environmental Protection, Department of General Biochemistry, Pomorska 141/143, 90-236 Lodz, Poland.
Article Synopsis
- - Multiple sclerosis (MS) is an autoimmune disease that leads to inflammation and damage to nerve tissues, and this study investigates the interactions between blood platelets and immune cells (leukocytes) in MS patients.
- - Researchers found that there is a significant increase in the movement of leukocytes towards platelets in MS, indicating that these immune interactions are enhanced, particularly in patients with relapsing-remitting MS (RRMS) and secondary progressive MS (SPMS).
- - The study highlights the importance of the CD40-CD40L pathway in the communication between platelets and B-cells, suggesting that this interaction may play a key role in the progression of MS and could be a target for future therapeutic strategies.
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