PGE limits effector expansion of tumour-infiltrating stem-like CD8 T cells.

Cancer-specific TCF1 stem-like CD8 T cells can drive protective anticancer immunity through expansion and effector cell differentiation; however, this response is dysfunctional in tumours. Current cancer immunotherapies can promote anticancer responses through TCF1 stem-like CD8 T cells in some but not all patients. This variation points towards currently ill-defined mechanisms that limit TCF1CD8 T cell-mediated anticancer immunity.

Rational design of PD-1-CD28 immunostimulatory fusion proteins for CAR T cell therapy.

Background: In many situations, the therapeutic efficacy of CAR T cells is limited due to immune suppression and poor persistence. Immunostimulatory fusion protein (IFP) constructs have been advanced as a tool to convert suppressive signals into stimulation and thus promote the persistence of T cells, but no universal IFP design has been established so far. We now took advantage of a PD-1-CD28 IFP as a clinically relevant structure to define key determinants of IFP activity.

Bispecific antibodies redirect synthetic agonistic receptor modified T cells against melanoma.

Background: Melanoma is an immune sensitive disease, as demonstrated by the activity of immune check point blockade (ICB), but many patients will either not respond or relapse. More recently, tumor infiltrating lymphocyte (TIL) therapy has shown promising efficacy in melanoma treatment after ICB failure, indicating the potential of cellular therapies. However, TIL treatment comes with manufacturing limitations, product heterogeneity, as well as toxicity problems, due to the transfer of a large number of phenotypically diverse T cells.

T cell-derived interleukin-22 drives the expression of CD155 by cancer cells to suppress NK cell function and promote metastasis.

Although T cells can exert potent anti-tumor immunity, a subset of T helper (Th) cells producing interleukin-22 (IL-22) in breast and lung tumors is linked to dismal patient outcome. Here, we examined the mechanisms whereby these T cells contribute to disease. In murine models of lung and breast cancer, constitutional and T cell-specific deletion of Il22 reduced metastases without affecting primary tumor growth.

Migratory Engineering of T Cells for Cancer Therapy.

Adoptive cell therapy (ACT) and chimeric antigen receptor (CAR) T cell therapy in particular represents an adaptive, yet versatile strategy for cancer treatment. Convincing results in the treatment of hematological malignancies have led to FDA approval for several CAR T cell therapies in defined refractory diseases. In contrast, the treatment of solid tumors with adoptively transferred T cells has not demonstrated convincing efficacy in clinical trials.

Polymer-Induced Drag Reduction in Dilute Newtonian and Semi-Dilute Non-Newtonian Fluids: An Assessment of the Double-Gap Concentric Cylinder Method.

Polymer-induced drag reduction (DR) in fluids was studied using a rotational rheometer with double-gap concentric cylinder geometry. Although both polymers (polyacrylamide (PAM) and 2-acrylamido-2-methylpropane sulfonic acid (SPAM)) had molecular weights of several MDa, the contrasting polymer charge, nonionic and anionic, led to different polymer overlap concentrations (*), PAM ≫ SPAM, and fluid rheology, with PAM fluids mostly Newtonian and SPAM fluids non-Newtonian (shear-thinning). Based on these differences, it was important to account for the infinite shear viscosity and normalize the polymer concentration by the intrinsic concentration ( ) so that the DR performance of the two polymer fluids could be accurately compared.

CAR T Cells Targeting Membrane-Bound Hsp70 on Tumor Cells Mimic Hsp70-Primed NK Cells.

Strategies to boost anti-tumor immunity are urgently needed to treat therapy-resistant late-stage cancers, including colorectal cancers (CRCs). Cytokine stimulation and genetic modifications with chimeric antigen receptors (CAR) represent promising strategies to more specifically redirect anti-tumor activities of effector cells like natural killer (NK) and T cells. However, these approaches are critically dependent on tumor-specific antigens while circumventing the suppressive power of the solid tumor microenvironment and avoiding off-tumor toxicities.