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PD1-TLR10 fusion protein enhances the antitumor efficacy of CAR-T cells in colon cancer.
Int Immunopharmacol
January 2025
TriArm Therapeutics, Niudun Road 200, 201203 Shanghai, China. Electronic address:
Background: The immunosuppressive microenvironment negatively affects the efficacy of chimeric antigen receptor T (CAR-T) cells in solid tumors. Fusion protein that combining extracellular domain of inhibitory checkpoint protein and the cytoplasmic domain of stimulatory molecule may improve the efficacy of CAR-T cells by reversing the suppressive signals.
Methods: To generate optimal PD1-TLR10 fusion proteins, PD1 extracellular domain and TLR10 intracellular domain were connected by transmembrane domain from PD1, CD28, or TLR10, respectively.
Mechanistic determinants and dynamics of cA6 synthesis in type III CRISPR-Cas effector complexes.
Nucleic Acids Res
January 2025
Department of Biochemistry, University of Zurich, Winterthurerstrass 190, 8057 Zurich, Switzerland.
Type III clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) systems (type III CRISPR-Cas systems) use guide RNAs to recognize RNA transcripts of foreign genetic elements, which triggers the generation of cyclic oligoadenylate (cOA) second messengers by the Cas10 subunit of the type III effector complex. In turn, cOAs bind and activate ancillary effector proteins to reinforce the host immune response. Type III systems utilize distinct cOAs, including cyclic tri- (cA3), tetra- (cA4) and hexa-adenylates (cA6).
View Article and Find Full Text PDFVδ2 T-cells response in people with Mpox infection: a three-month longitudinal assessment.
Emerg Microbes Infect
January 2025
HIV/AIDS Unit, National Institute for Infectious Diseases "Lazzaro Spallanzani" IRCCS, Rome, Italy.
The first evidence that Orthopoxvirus induced the expansion and the recall of effector innate Vδ2T-cells was described in a macaque model. Although, an engagement of αβ T-cells specific response in patients infected with human monkeypox (Mpox) was demonstrated, little is known about the role of γδ T-cells during Mpox infection. IFN-γ-producing γδ T-cells in the resistance to poxviruses may a key role in inducing a protective type 1 memory immunity.
View Article and Find Full Text PDFIntegrating T-cell inflammation features for prognosis in hepatocellular carcinoma: a novel predictive model.
J Gastrointest Oncol
December 2024
Department of Hepatobiliary Surgery, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, China.
Background: Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death globally and accounts for 75% to 90% of primary liver cancer cases. The high mortality rate of HCC, coupled with the absence of reliable prognostic biomarkers, makes its treatment and prognosis evaluation challenging. The features of the T cell-inflamed microenvironment include active interferon (IFN)-γ signaling and the presence of cytotoxic effector molecules, antigen presentation, and T-cell activating cytokines.
View Article and Find Full Text PDFAlveolar type 2 (AT2) cells maintain lung health by acting as stem cells and producing pulmonary surfactant. AT2 dysfunction underlies many lung diseases, including interstitial lung disease (ILD), in which some inherited forms result from the mislocalization of surfactant protein C (SFTPC) variants. Lung disease modeling and dissection of the underlying mechanisms remain challenging due to complexities in deriving and maintaining human AT2 cells ex vivo.
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