Publications by authors named "Javier A Pinilla-Ibarz"
Article Synopsis
- - The study investigates the challenges faced by patients with diffuse large B-cell lymphoma (DLBCL) treated with CD19 CAR T-cell therapy, highlighting poor outcomes associated with this treatment.
- - Researchers identified specific serum proteins linked to severe immune-related toxicities and worse clinical responses, leading to a new risk stratification tool using pre-lymphodepletion C reactive protein (CRP) and ferritin levels.
- - Validated with international cohorts, the findings suggest that this easy-to-use model can effectively classify patients by risk and improve decision-making for CAR T-cell therapy, optimizing patient selection.
Activation-induced cytidine deaminase (AID) has been implicated as both a positive and a negative factor in the progression of B cell chronic lymphocytic leukemia (CLL), but the role that it plays in the development and progression of this disease is still unclear. We generated an AID knockout CLL mouse model, AID/Eμ-TCL1, and found that these mice die significantly earlier than their AID-proficient counterparts. AID-deficient CLL cells exhibit a higher ER stress response compared to Eμ-TCL1 controls, particularly through activation of the IRE1/XBP1s pathway.
View Article and Find Full Text PDFArticle Synopsis
- STING is an important protein in B cells that senses cytoplasmic DNA and typically helps produce type I interferons, but its role in B cell receptor (BCR) signaling was previously unclear.
- Researchers created mice with a specific STING mutation and discovered that activated STING in B cells led to the degradation of critical proteins, reducing their ability to respond to BCR activation and produce antibodies.
- The study also found that STING downregulation in chronic lymphocytic leukemia (CLL) cells contributed to enhanced BCR signaling, indicating that STING negatively regulates BCR signaling in both healthy and cancerous B cells.
Article Synopsis
- Venetoclax-based therapy is a standard treatment for chronic lymphocytic leukemia (CLL), but how to manage patients after stopping it is unclear.
- A study involving 326 patients who discontinued venetoclax explored their responses to different treatments, focusing on overall response rate and progression-free survival.
- Results indicated that BTK inhibitors were highly effective for patients who had not previously received them, while less effective for those who had, and PI3K inhibitors provided limited benefit, highlighting the importance of treatment history when selecting post-venetoclax therapies.
Article Synopsis
- Activation of the ER stress response is linked to the worsening of B cell chronic lymphocytic leukemia (CLL), and researchers found that mice lacking the XBP-1 factor showed slowed disease progression.
- The absence of XBP-1 led to traits that made leukemic cells less viable, such as weakened BCR signaling and higher levels of a specific receptor (S1P1) on their surface.
- A new chemical inhibitor, B-I09, effectively mimicked XBP-1 deficiency, reducing leukemic progression in treated mice and showing potential as a treatment combined with an existing leukemia drug, ibrutinib, with no major side effects.
Article Synopsis
- Chronic lymphocytic leukemia (CLL) accounts for 30% of adult leukemia cases, with TCL1 expression found in about 90% of human CLL, and transgenic models show that TCL1 can induce CLL in mice.
- The study reveals that the endoplasmic reticulum (ER) stress response is abnormally activated in both Eμ-TCL1 mouse models and human CLL, indicating a connection between TCL1 and certain transcription factors that lead to disease progression.
- By inhibiting the IRE-1/XBP-1 pathway, researchers observed that CLL cells experienced apoptosis and halted growth, suggesting that targeting the ER stress response could be a novel treatment strategy for CLL.
Article Synopsis
- * Research suggests that using methylation inhibitors, like 5-aza-2'-deoxycytidine (5A2), may help alter T cell polarization, specifically by inducing changes that lead to more effective immune responses.
- * The study showed that 5A2 can successfully shift T cells towards a Th1 polarization, which might offer new therapeutic strategies to improve T cell function in CLL patients.
Article Synopsis
- Tyrosine kinase inhibitors (TKIs) are the preferred treatment for chronic myelogenous leukemia (CML), but they can cause unique side effects due to off-target kinase inhibition.
- A study of 64 CML patients on different TKIs found that while all groups had clonal expansions of cytotoxic T lymphocytes (CTLs), only those treated with dasatinib showed expansions of large granular lymphocytes (LGLs).
- Factors associated with LGL leukemia were linked to these expansions, and patients with LGLs exhibited increased cytotoxicity against normal endothelial cells, potentially explaining some autoimmune-like reactions observed during treatment.
Article Synopsis
- - Chronic lymphocytic leukemia (CLL) originates from B-lymphocytes but loses their ability to present antigens, leading to T-cell dysfunction and immune suppression.
- - Treatment with the demethylating agent 5-aza-2'-deoxycytidine has previously shown to enhance antigen expression in CLL cells.
- - The combination of 5-aza-2'-deoxycytidine and the histone deacetylase inhibitor LAQ824 restores the immune function of CLL cells, promoting T-cell activation and suggesting a new immunotherapy approach for CLL patients.
Article Synopsis
- The study focuses on identifying cancer-specific proteins, particularly cancer testis antigens (CTAs), which are key for developing effective immunotherapy against cancer, especially in chronic lymphocytic leukemia (CLL).
- Researchers evaluated the immunogenicity of 29 CTAs in CLL patients and found significant antibody responses to one antigen, NXF2, after treatment with 5-aza-2'-deoxycytidine, which also enhanced antigen presentation capabilities.
- The findings highlight the potential of NXF2 as an immunotherapy target for CLL and suggest that demethylating treatments can effectively alter CTA expression in cancer cells for better immune responses.