LAG-3 and 4-1BB identify dysfunctional antigen-specific T cells in the tumor microenvironment and combinatorial LAG-3/4-1BB targeting gives synergistic tumor control
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منابع مشابه
LAG-3 and 4-1BB identify dysfunctional antigen-specific T cells in the tumor microenvironment and combinatorial LAG-3/4-1BB targeting gives synergistic tumor control
Although the presence of tumor-infiltrating lymphocytes (TILs) indicates an endogenous anti-tumor response, immune regulatory pathways can subvert the effector phase and enable tumor escape. One possible negative regulatory pathway is T cell-intrinsic anergy. Recently, we have shown that the transcription factor Egr2 is critical in controlling the anergic state using an in vitro model system. G...
متن کاملThe EGR2 targets LAG-3 and 4-1BB describe and regulate dysfunctional antigen-specific CD8+ T cells in the tumor microenvironment
Although the presence of tumor-infiltrating lymphocytes (TILs) indicates an endogenous antitumor response, immune regulatory pathways can subvert the effector phase and enable tumor escape. Negative regulatory pathways include extrinsic suppression mechanisms, but also a T cell-intrinsic dysfunctional state. A more detailed study has been hampered by a lack of cell surface markers defining tumo...
متن کاملAgonist anti-4-1BB plus neutralizing anti-CTLA-4 or -PD-L1 synergize to promote tumor regression by rescuing dying dysfunctional CD8+ T cells within the tumor microenvironment
Tumors can be broadly placed into two categories: those that are T cell-inflamed and those that are not, with T cell-inflamed tumors having specific chemokine and type I interferon gene expression signatures as well as CD8 tumor-infiltrating T cells (TIL). The fact that these T cell-inflamed tumors are not destroyed by the CD8 TIL argues that mechanisms in the tumor microenvironment must render...
متن کاملMultivalent 4-1BB binding aptamers costimulate CD8+ T cells and inhibit tumor growth in mice.
4-1BB is a major costimulatory receptor that promotes the survival and expansion of activated T cells. Administration of agonistic anti-4-1BB Abs has been previously shown to enhance tumor immunity in mice. Abs are cell-based products posing significant cost, manufacturing, and regulatory challenges. Aptamers are oligonucleotide-based ligands that exhibit specificity and avidity comparable to, ...
متن کاملAgonistic 4-1bb antibodies in combination with inhibitory antibodies against CTLA-4, PD-L1 or LAG-3 ACT on CD8+ T cells in the tumor microenvironment and synergize to promote regression of established tumors
Tumors can be placed into two categories: those that are T cell-inflamed and those that are not, based on specific chemokine and type I interferon gene expression signatures and CD8 tumor infiltrating T cells (TIL). That these immune-inflamed tumors are not destroyed by the CD8 TIL argues that mechanisms must be present to render the CD8 TIL dysfunctional. Baseline infiltration of CD8 T cells a...
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ژورنال
عنوان ژورنال: Journal for ImmunoTherapy of Cancer
سال: 2015
ISSN: 2051-1426
DOI: 10.1186/2051-1426-3-s2-p328