A novel combination of chemotherapy and immunotherapy controls tumor growth in mice with a human immune system

Abstract

Mice reconstituted with a human immune system and bearing human tumors represent a promising model for developing novel cancer immunotherapy strategies. However, the nature of tumor infiltrating leukocytes in humanized mice and whether they can be mobilized to control tumor growth is currently unknown. Here, we used mass cytometry and multi parametric flow cytometry to characterize human leukocytes infiltrating a human breast cancer tumor model in CD34-reconstituted NOD.SCID.gc-null mice and compared it to breast cancer patient's samples. We unambiguously detected human T cells,

Circulating Treg cells from patients with cerebral aneurysms displayed deficiency in ICOS expression and function

“…Inducible costimulator (ICOS) is a member of the CD28 family and is expressed on both Tconv cells and Treg cells 18,19 . In Treg cells, the interaction between ICOS and its ligand ICOSL is necessary for the optimal expression of Foxp3, 20 while Treg cells with ICOS‐knockout present stronger methylation at the CNS2 region of the Foxp3 gene 18 .…”

Recruitment and Expansion of Tregs Cells in the Tumor Environment—How to Target Them?

“…Indeed, their proliferation is completely blocked by the addition of antagonist mAbs directed against ICOS or ICOS-L. In addition, in a humanized mouse model of breast carcinoma, the addition of a neutralizing anti-ICOS mAb reduced the Treg proportion and improved the CD4 + T cell proliferation [ 164 ].…”

“…However, Mo et al [ 365 ] recently demonstrated, in a mouse prostate tumor model, that ICOS + Treg depletion with an antagonist mAb strongly increased the efficacy of GM-CSF-modified cancer cell vaccine. In the same way, Burlion et al recently reported, in humanized mice with breast tumors, that a combination of neutralizing anti-ICOS mAb and chemotherapy controls tumor growth by reducing the Treg proportion and increasing the CD8 + T cell/Treg ratio in the TME [ 164 ]. Therefore, depleting the TA-Tregs with the ICOS antagonist might be a promising immunotherapy strategy.…”

Co-stimulatory agonists: An insight into the immunotherapy of cancer

“…Nevertheless, when utilized together with other strategies, especially when combined with CTLA-4 blockade it contributes to a robust synergistic effect which are attributed to the increase in ICOS expression post- anti-CTLA-4 therapy (Table 5 (Tab. 5) ; References in Table 5: Burlion et al, 2019[ 11 ]; Carrell et al, 2018[ 12 ]; Harvey et al, 2015[ 30 ]; Sanmamed et al, 2015[ 83 ]; Zamarin et al, 2017[ 105 ]).…”

“…The depletion of human CD8 + T cells or of murine myeloid cells slightly influenced the efficiency of combination strategy. These findings suggested that when anti-ICOS mAbs are combined with chemotherapy, it controlled tumor growth in humanized mice and opened up horizons in treating breast cancer (Burlion et al, 2019[ 11 ]). Electrochemotherapy is a growing therapeutic approach which has recently been claimed to cause an immunogenic form of cell death.…”