Background T cells are part of the immune system’s adaptive defence; they specifically target and kill both virally infected and cancerous cells through antigen recognition. Unfortunately, cancer can exploit intrinsic T cell mechanisms to survive attack by the immune system. T cell exhaustion arises from chronic antigen stimulation, which shifts a portion of the T… Continue reading 1124 Discovering transcriptional regulators of T cell exhaustion for epigenetic reversal of T cell dysfunction
Tag: Nucleic Acid Biochemistry
1112 Sticky T cells: engineered T cells targeting biglycan on tumor endothelial cells enhance infiltration into metastatic tumors
Background Poor infiltration of therapeutic cells to solid tumors is a major hurdle to success of cell-based therapies.1Upon intravenous administration, only a small fraction (<2%) of these cells infiltrate the tumor.2 3 One of the mechanisms driving exclusion of immune cells from solid tumors is the endothelial cell anergy of angiogenic vessels. Angiogenic vessels have… Continue reading 1112 Sticky T cells: engineered T cells targeting biglycan on tumor endothelial cells enhance infiltration into metastatic tumors
1018 Leveraging innate immune sensors to generate durable anti-glioma adaptive immune responses
Background Glioblastoma harbors a tumor microenvironment (TME) that is mostly devoid of effector T cells but is dominated by immunosuppressive microglia, macrophages, and myeloid-derived suppresser cells. Innate immune cells in the TME have impaired phagocytosis and antigen presentation and are inadequate for triggering the immune activating signals needed for anti-tumor effector responses. Glioblastoma tumors further… Continue reading 1018 Leveraging innate immune sensors to generate durable anti-glioma adaptive immune responses
1011 Metabolic reprogramming alters natural killer cell responses in chronic graft-versus-host disease
Background Allogeneic hematopoietic stem cell transplantation (HSCT) has been developed as a major treatment option for leukemia and lymphoma patients. HSCT transfers pluripotent stem cells to reconstitute patients’ hematopoiesis with functional immune cells. Although the clinical practice of HSCT has been extensively studied and significantly improved over the last decades, the leading cause of late… Continue reading 1011 Metabolic reprogramming alters natural killer cell responses in chronic graft-versus-host disease
934 ZFP148 represses effector differentiation and cytotoxicity of CD8+ T cells during chronic viral infection and cancer
Background In both chronic virus infection and cancer settings, antigen-experienced CD8+ T cell can differentiate into either effector or exhausted branches. While transcriptional and epigenetic control of the development of exhausted CD8+ T cells are relatively well-described,1 2 little is known about how the generation and maintenance of the effector population is regulated. Zinc-Finger Protein… Continue reading 934 ZFP148 represses effector differentiation and cytotoxicity of CD8+ T cells during chronic viral infection and cancer
927 Investigating the role of hypomethylating agents in ameliorating T cell exhaustion in acute myeloid leukemia
Background Acute myeloid leukemia (AML) is a lethal adult hematologic malignancy with a 5-year survival rate of 30%. The standard of care is cytotoxic chemotherapy which often results in remission, but most patients relapse. Recent findings support a rationale that immunotherapy may hold promise as a treatment for this malignancy. Our lab has shown that… Continue reading 927 Investigating the role of hypomethylating agents in ameliorating T cell exhaustion in acute myeloid leukemia
918 The signal strength of signal 2 and 3 during T cell priming affect the functional fate of an anti-tumor T cell response
Background CD8+ T cell fate decision refers to the differentiation of a naïve T cell into effector, memory, exhausted, or other fates. Evidence from chronic infection and cancer models suggest that signals during T cell priming are especially important in determining T cell fate and thus the functional quality of the T cell response.1–4 Priming… Continue reading 918 The signal strength of signal 2 and 3 during T cell priming affect the functional fate of an anti-tumor T cell response
874 Epigenetic modulation of myeloid derived suppressor cells decreases suppressive signaling through the STAT3 pathway
Background Immune checkpoint inhibitors (ICIs) have shown promise in managing various cancers and improving patient quality of life. However, patients with metastatic breast cancer are considered intrinsically or eventually resistant. A proposed mechanism of resistance to ICIs is the extensive infiltration of the tumor microenvironment (TME) with immunosuppressive cells, such as myeloid derived suppressor cells… Continue reading 874 Epigenetic modulation of myeloid derived suppressor cells decreases suppressive signaling through the STAT3 pathway
867 Tumor-derived nutrient stress induces lasting effects on CD8+ T cell function and epigenetic remodeling
Background In tumors, CD8 T cells are exposed to metabolically active environments where certain nutrients are scarce. The tumor nutrient environment shapes T cell responses, but little is known about the long-term, heritable effects of tumor nutrient stress on CD8 T cells. To examine the heritable effects of nutrient stress, CD8 T cells were cultured… Continue reading 867 Tumor-derived nutrient stress induces lasting effects on CD8+ T cell function and epigenetic remodeling
827 Viroimmunotherapy combined with acetylation suppression: advanced therapeutics for pediatric diffuse midline gliomas
Background Oncolytic virotherapy is a special case of cancer immunotherapy that mounts a significant inflammatory immune response along with oncolysis. We recently demonstrated that Delta-24-RGD, an oncolytic adenovirus, can be safely combined with radiotherapy to treat pediatric Diffuse Intrinsic Pontine Glioma in a phase I clinical trial (NCT03178032). In this trial, combining Delta-24-RGD with radiotherapy… Continue reading 827 Viroimmunotherapy combined with acetylation suppression: advanced therapeutics for pediatric diffuse midline gliomas