Immuno-Oncology: T-cells targeting and killing cancer cells

The relationship between immune system and cancer is elaborated and dynamic.

Immunotherapy has been acquiring big visibility in recent years and even more in the last months thanks to the 2018 Nobel Prize for medicine (read here). Immunotherapy involves re-engineering T-cells so that they can recognize and kill cancer cells. This type of therapy has shown promising preliminary results in fighting lymphoma.

Microscopy is the elected method to study immune cells interactions and their potential for cancer healing. However, technologies that are available nowadays mainly rely on fluorescence, and fragile primary immune cells are heavily perturbed and eventually killed by staining procedures and phototoxicity.

The research on immune-oncology will greatly benefit from a high-resolution, label-free approach allowing to image immune cells interplays in a marker-free, non-invasive way.

Nanolive’s 3D Cell Explorer opens the door for new observations and for long-term live cell imaging (up to weeks of continuous imaging) with unprecedented spatio-temporal resolution (<200nm; 1img/2sec).

Video 1: T-cell activation: APC cells (Macrophages and dendritic cells obtained after isolation and in vitro differentiation of bone marrow cells from C57BL/6 mice) were incubated with freshly isolated naïve T cells and imaged with Nanolive’s 3D Cell Explorer for 11 minutes at a frequency of 1 image every 10 seconds

APC T-cell interaction/activation experiment

In the first movie obtained with Nanolive’s 3D Cell Explorer, we can witness to the T-Cell activation process totally marker-free. Pre-stimulated antigen presenting cells (APCs*: dendritic cells and macrophages) are cultured with freshly isolated “naïve T-cells”, the OT-I mice T-cells in order to teach them to recognize and kill tumor cells.

* APCs are special cells that present the antigens on their surface so that other immune cells can “see” and detect it.

T-cells killing cancer cells

In this movie and in the zoom-in below you can see T-Cells killing cancer cells.
The cancer cell line is MC38-OVA, a transduced colon cancer cell line that expresses the ovalbumin (OVA) model antigen.

T-cells, coming from OT-I mice, carry a transgenic T-cell receptor responsive to OVA residues 257-264 (SIINFEKL peptide) in the context of the MHC I H2kb.

In this experiment, the T-cells that were activated in the first experiment and that are now called “effectors”, are incubated with MC38-OVA cancer cells. Upon recognition of their target (the OVA residues on the MHC I H2kB of the cancer cells), T-cells induce the killing of the cancer cells. However, this does not happen all the time and many cancer cells survive.

*Clarke et al. 2000, Immune Cell Biol (https://onlinelibrary.wiley.com/doi/full/10.1046/j.1440-1711.2000.00889.x).

Video 2: Activated T-cells were incubated against the OVA antigen were incubated with MC38-OVA cancer cells expressing the OVA antigen. Cells were imaged for over 6hours at a frequency of 1 image every 20 seconds

Cut of Video 2 zooming on one specific cell. Left panel: 2D Refractive index map and on the right panel 3D reconstruction obtained through digital stain

Video 4: Cut of Video 2 zooming on one specific cell

A special thanks goes to Chiara Cianciaruso from the UPDEPALMA lab at EPFL for preparing the cells for us 🙂

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