36 research outputs found
TIGIT/CD226 Axis Regulates Anti-Tumor Immunity
Tumors escape immune surveillance by inducing various immunosuppressive pathways, including the activation of inhibitory receptors on tumor-infiltrating T cells. While monoclonal antibodies (mAbs) blocking programmed cell death 1 (PD-1), programmed death-ligand 1 (PD-L1), and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) have been approved for multiple cancer indications, only a subset of patients benefit from immune checkpoint blockade therapies, highlighting the need for additional approaches. Therefore, the identification of new target molecules acting in distinct or complementary pathways in monotherapy or combination therapy with PD-1/PD-L1 blockade is gaining immense interest. T cell immunoreceptor with Ig and immunoreceptor tyrosine-based inhibitory motif (ITIM) domains (TIGIT) has received considerable attention in cancer immunotherapy. Recently, anti-TIGIT mAb (tiragolumab) has demonstrated promising clinical efficacy in non-small cell lung cancer treatment when combined with an anti-PD-L1 drug (Tecentriq), leading to phase III trial initiation. TIGIT is expressed mainly on T and natural killer cells; it functions as an inhibitory checkpoint receptor, thereby limiting adaptive and innate immunity. CD226 competes for binding with the same ligands with TIGIT but delivers a positive stimulatory signal to the immune cells. This review discusses the recent discoveries regarding the roles of TIGIT and CD226 in immune cell function and their potential application in cancer immunotherapy
TIGIT/CD226 Axis Regulates Anti-Tumor Immunity
Tumors escape immune surveillance by inducing various immunosuppressive pathways, including the activation of inhibitory receptors on tumor-infiltrating T cells. While monoclonal antibodies (mAbs) blocking programmed cell death 1 (PD-1), programmed death-ligand 1 (PD-L1), and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) have been approved for multiple cancer indications, only a subset of patients benefit from immune checkpoint blockade therapies, highlighting the need for additional approaches. Therefore, the identification of new target molecules acting in distinct or complementary pathways in monotherapy or combination therapy with PD-1/PD-L1 blockade is gaining immense interest. T cell immunoreceptor with Ig and immunoreceptor tyrosine-based inhibitory motif (ITIM) domains (TIGIT) has received considerable attention in cancer immunotherapy. Recently, anti-TIGIT mAb (tiragolumab) has demonstrated promising clinical efficacy in non-small cell lung cancer treatment when combined with an anti-PD-L1 drug (Tecentriq), leading to phase III trial initiation. TIGIT is expressed mainly on T and natural killer cells; it functions as an inhibitory checkpoint receptor, thereby limiting adaptive and innate immunity. CD226 competes for binding with the same ligands with TIGIT but delivers a positive stimulatory signal to the immune cells. This review discusses the recent discoveries regarding the roles of TIGIT and CD226 in immune cell function and their potential application in cancer immunotherapy
TAIL-seq for X. laevis wild-type early embryos replicate set #1 (internal ID: hs27, part 5/12)
<p>This dataset contains the raw sequencing data from a TAIL-seq run for Xenopus laevis embryos. The cluster intensities of fluorescence signals are repacked as an HDF5 formatted file, then split into multiple parts to fit in the dataset size limitation of the Zenodo.</p
Deletion of Human tarbp2 Reveals Cellular MicroRNA Targets and Cell-Cycle Function of TRBP
TRBP functions as both a Dicer cofactor and a PKR
inhibitor. However, the role of TRBP in microRNA
(miRNA) biogenesis is controversial and its regulation
of PKR in mitosis remains unexplored. Here,
we generate TRBP knockout cells and find altered
Dicer-processing sites in a subset of miRNAs but
no effect on Dicer stability, miRNA abundance, or
Argonaute loading. By generating PACT, another
Dicer interactor, and TRBP/PACT double knockout
(KO) cells, we further show that TRBP and PACT do
not functionally compensate for one another and
that only TRBP contributes to Dicer processing. We
also report that TRBP is hyperphosphorylated by
JNK in M phase when PKR is activated by cellular
double-stranded RNAs (dsRNAs). Hyperphosphorylation
potentiates the inhibitory activity of TRBP on
PKR, suppressing PKR in M-G1 transition. By generating
human TRBP KO cells, our study clarifies the
role of TRBP and unveils negative feedback regulation
of PKR through TRBP phosphorylation.138391sciescopu
Deletion of human tarbp2 reveals cellular microRNA targets and cell-cycle function of TRBP
TRBP functions as both a Dicer cofactor and a PKR inhibitor. However, the role of TRBP in microRNA (miRNA) biogenesis is controversial and its regulation of PKR in mitosis remains unexplored. Here, we generate TRBP knockout cells and find altered Dicer-processing sites in a subset of miRNAs but no effect on Dicer stability, miRNA abundance, or Argonaute loading. By generating PACT, another Dicer interactor, and TRBP/PACT double knockout (KO) cells, we further show that TRBP and PACT do not functionally compensate for one another and that only TRBP contributes to Dicer processing. We also report that TRBP is hyperphosphorylated by JNK in M phase when PKR is activated by cellular double-stranded RNAs (dsRNAs). Hyperphosphorylation potentiates the inhibitory activity of TRBP on PKR, suppressing PKR in M-G1 transition. By generating human TRBP KO cells, our study clarifies the role of TRBP and unveils negative feedback regulation of PKR through TRBP phosphorylation
TAIL-seq for X. laevis wild-type early embryos replicate set #1 (internal ID: hs27, part 4/12)
<p>This dataset contains the raw sequencing data from a TAIL-seq run for Xenopus laevis embryos. The cluster intensities of fluorescence signals are repacked as an HDF5 formatted file, then split into multiple parts to fit in the dataset size limitation of the Zenodo.</p
TAIL-seq for X. laevis wild-type early embryos replicate set #1 (internal ID: hs27, part 6/12)
<p>This dataset contains the raw sequencing data from a TAIL-seq run for Xenopus laevis embryos. The cluster intensities of fluorescence signals are repacked as an HDF5 formatted file, then split into multiple parts to fit in the dataset size limitation of the Zenodo.</p
TAIL-seq for X. laevis wild-type early embryos replicate set #1 (internal ID: hs27, part 10/12)
<p>This dataset contains the raw sequencing data from a TAIL-seq run for Xenopus laevis embryos. The cluster intensities of fluorescence signals are repacked as an HDF5 formatted file, then split into multiple parts to fit in the dataset size limitation of the Zenodo.</p