High-throughput method to analyze the cytotoxicity of CAR-T Cells in a 3D tumor spheroid model using image cytometry.

Solid tumors account for approximately 90% of all adult human cancers. As such, the development of novel cellular therapies has become of increasing importance to target solid tumor malignancies, such as prostate, lung, breast, bladder, colon, and liver cancers. One such cellular therapy relies on the use of chimeric antigen receptor T cells (CAR-T cells).

Tim-3 mediates T cell trogocytosis to limit antitumor immunity.

T cell immunoglobulin mucin domain-containing protein 3 (Tim-3) negatively regulates innate and adaptive immunity in cancer. To identify the mechanisms of Tim-3 in cancer immunity, we evaluated the effects of Tim-3 blockade in human and mouse melanoma. Here, we show that human programmed cell death 1-positive (PD-1+) Tim-3+CD8+ tumor-infiltrating lymphocytes (TILs) upregulate phosphatidylserine (PS), a receptor for Tim-3, and acquire cell surface myeloid markers from antigen-presenting cells (APCs) through transfer of membrane fragments called trogocytosis.

IL15 Stimulation with TIGIT Blockade Reverses CD155-mediated NK-Cell Dysfunction in Melanoma.

Purpose: Natural killer (NK) cells play a critical role in tumor immunosurveillance. Multiple activating and inhibitory receptors (IR) regulate NK-cell-mediated tumor control. The IR T-cell immunoglobulin and ITIM domain (TIGIT) and its counter-receptor CD226 exert opposite effects on NK-cell-mediated tumor reactivity.

Phase Ib/II Study of Pembrolizumab and Pegylated-Interferon Alfa-2b in Advanced Melanoma.

Purpose: Objective responses are reported in 34% to 37% of patients with programmed death-1 (PD-1)-naïve advanced melanoma treated with PD-1 inhibitors. Pre-existing CD8+ T-cell infiltrate and interferon (IFN) gene signature correlate with response to PD-1 blockade. Here, we report a phase Ib/II study of pembrolizumab/pegylated (PEG)-IFN combination in PD-1-naïve advanced melanoma.

CD226 opposes TIGIT to disrupt Tregs in melanoma.

CD4+ Tregs impede T cell responses to tumors. They express multiple inhibitory receptors that support their suppressive functions, including T cell Ig and ITIM domain (TIGIT). In melanoma patients, we show that Tregs exhibit increased TIGIT expression and decreased expression of its competing costimulatory receptor CD226 as compared with CD4+ effector T cells, resulting in an increased TIGIT/CD226 ratio.

Imbalance of circulating lymphoid cells in Q fever endocarditis.

Q fever endocarditis is characterized by a defective cell-mediated immune response, which may be associated with the dysregulation of circulating subsets of immune cells. In this study, we found that naïve CD8(+) T lymphocytes and CD56dim natural killer cells were decreased patients whereas central memory CD8(+) T lymphocytes were increased. It is likely that these different subsets of immune cells play a role in the immunosuppression accompanying Q fever endocarditis.

Programmed death ligand-1 expression and memory T-cell generation in Coxiella burnetii infection.

Programmed death ligand-1 (PD-L1) is a co-signaling molecule that regulates T-cell responses in vivo. Its role in bacterial infections, including Q fever, a zoonosis due to Coxiella burnetii infection, is not well understood. We showed by flow cytometry that PD-L1 membrane expression was specifically increased in T-cells from patients with acute Q fever, not from patients with Q fever endocarditis, suggesting that PD-L1 plays a role in the early phases of C.

Myeloid decidual dendritic cells and immunoregulation of pregnancy: defective responsiveness to Coxiella burnetii and Brucella abortus.

Dendritic cells (DCs) are a component of the placental immune system, but their role in pregnancy is still poorly understood. Decidual DCs (dDCs) were selected from at-term pregnancy on the basis of CD14 and CD11c expression. A phenotypic analysis revealed that dDCs are characterized by the expression of monocyte-derived DC (moDCs) markers and specific markers such as HLA-G and its ligand ILT4.

Phenotypic diversity and emerging new tools to study macrophage activation in bacterial infectious diseases.

Macrophage polarization is a concept that has been useful to describe the different features of macrophage activation related to specific functions. Macrophage polarization is responsible for a dichotomic approach (killing vs. repair) of the host response to bacteria; M1-type conditions are protective, whereas M2-type conditions are associated with bacterial persistence.

Imbalance of circulating monocyte subsets and PD-1 dysregulation in Q fever endocarditis: the role of IL-10 in PD-1 modulation.

Q fever endocarditis, a severe complication of Q fever, is associated with a defective immune response, the mechanisms of which are poorly understood. We hypothesized that Q fever immune deficiency is related to altered distribution and activation of circulating monocyte subsets. Monocyte subsets were analyzed by flow cytometry in peripheral blood mononuclear cells from patients with Q fever endocarditis and controls.

Intracellular bacteria interfere with dendritic cell functions: role of the type I interferon pathway.

Dendritic cells (DCs) orchestrate host defenses against microorganisms. In infectious diseases due to intracellular bacteria, the inefficiency of the immune system to eradicate microorganisms has been attributed to the hijacking of DC functions. In this study, we selected intracellular bacterial pathogens with distinct lifestyles and explored the responses of monocyte-derived DCs (moDCs).