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T-Cell Exhaustion Signatures Vary with Tumor Type and Are Severe in Glioblastoma
- K. Woroniecka, Pakawat Chongsathidkiet, +19 authors P. Fecci
- MedicineClinical Cancer Research
- 7 February 2018
The poor TIL function and severe exhaustion observed in GBM highlight the need to better understand this tumor-imposed mode of T-cell dysfunction in order to formulate effective immunotherapeutic strategies targeting GBM.
Systemic Anti-CD25 Monoclonal Antibody Administration Safely Enhances Immunity in Murine Glioma without Eliminating Regulatory T Cells
Systemic anti-CD25 administration does not entirely eliminate Tregs but does prevent Treg function, which leads to safe enhancement of tumor immunity in a murine glioma model that recapitulates the tumor-induced changes to the CD4 and Treg compartments seen in patients with malignant gliomas.
Transfer of allogeneic CD62L- memory T cells without graft-versus-host disease.
A novel strategy to selectively prevent GVHD by depleting CD62L(+) T cells (naive and a subset of memory T cells) by allowing transfer of allogeneic recall antitumor and antimicrobial immunity without causing graft-versus-host disease.
Growth hormone accelerates immune recovery following allogeneic T-cell-depleted bone marrow transplantation in mice.
It is demonstrated that recombinant human growth hormone can accelerate phenotypic and functional immune reconstitution following allogeneic T-cell-depleted bone marrow transplantation in mice.
Monoclonal antibody blockade of IL-2 receptor α during lymphopenia selectively depletes regulatory T cells in mice and humans.
This is the first report of systemic antibody-mediated T(Reg) depletion during lymphopenia and the consequent synergistic enhancement of vaccine-driven cellular responses, as well as the first demonstration that anti-IL-2Rα mAbs function differentially in nonlymphopenic versus lymphopenic contexts.
Sequestration of T-cells in bone marrow in the setting of glioblastoma and other intracranial tumors
It is revealed that even treatment-naïve subjects and mice with GBM can harbor AIDS-level CD4 counts, as well as contracted, T cell–deficient lymphoid organs, and sequestration of T cells in bone marrow is a tumor-adaptive mode of T cell dysfunction, whose reversal may constitute a promising immunotherapeutic adjunct.
Prevention of graft-versus-host disease while preserving graft-versus-leukemia effect after selective depletion of host-reactive T cells by photodynamic cell purging process.
The data suggest that PDP can selectively deplete host alloantigen-specific T cells for GVHD prevention and immune and antileukemia function preserve.
Selective modification of antigen-specific T cells by RNA electroporation.
- D. Mitchell, I. Karikari, X. Cui, W. Xie, R. Schmittling, J. Sampson
- Biology, MedicineHuman gene therapy
- 28 May 2008
These studies demonstrate the utility of RNA transfection as a simple method by which to purify and selectively modify the function of antigen-specific T cells for use in adoptive immunotherapy and provide evidence that transient expression of proteins by RNAtransfection is an efficient means of modulating the in vivo function of activated T cells.
Hematopoietic stem cell dose correlates with the speed of immune reconstitution after stem cell transplantation.
Higher numbers of total thymocytes and signal joint T-cell receptor excision circles were observed in the higher dose stem cell recipients, suggesting that accelerated regeneration of T cells was due to enhanced thymopoiesis.
Addition of a second, different allogeneic graft accelerates white cell and platelet engraftment after T-cell-depleted bone marrow transplantation.
The data suggest that combining stem cells from MHC-mismatched allogeneic donors is feasible, that it has beneficial effects on myeloid engraftment and T-cell phenotypic recovery, and that the long-term stable mixed chimeras are immunologically normal following T- cell-depleted bone marrow transplantation.