Immuno-Oncology: The Relationship Between the Immune System and Cancer

The relationship between cancer and the immune system is dynamic and elaborated. In recent years, and even more so in the last few months, immunotherapy has been gaining huge visibility thanks to the 2018 Nobel Prize for medicine. Immunotherapy consists of re-engineering T-cells so that they can identify and eradicate cancer cells. This method of therapy has shown promising preliminary results in combating lymphoma.

Microscopy is the chosen technique to study immune cell interactions and their capability for the healing of cancer. Yet, the technologies which are available today rely largely on fluorescence, and fragile primary immune cells can be heavily perturbed and eventually killed by phototoxicity and staining procedures.

The research on immune-oncology will benefit massively from a label-free, high-resolution approach permitting imaging of immune cells interplays in a non-invasive, marker-free way. Nanolive’s 3D Cell Explorer paves the way for new observations and for long-term live cell imaging (weeks of continuous imaging) with unprecedented spatio-temporal resolution (<200 nm; 1 img/2 sec).

APC T-Cell Interaction/Activation Experiment

We can observe the T-Cell activation process completely marker-free in the first movie obtained with Nanolive’s 3D Cell Explorer. 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 train 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.

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

T-Cells Killing Cancer Cells

In this video and in the zoom-in you can observe 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.

The T-cells that were activated in the first experiment and that are now called “effectors,” are incubated with MC38-OVA cancer cells in this experiment. T-cells induce the killing of the cancer cells upon identification of their target (the OVA residues on the MHC I H2kB of the cancer cells). Yet, this does not occur every time and a number of 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

Video 3. 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

The Nobel Prize in Physiology or Medicine 2018

Discovery of Cancer Therapy by Inhibition of Negative Immune Regulation by James P. Allison & Tasuku Ho

Nanolive would like to congratulate the 2018 Nobel Prize in Physiology or Medicine which was awarded to Tasuku Honjo and James P. Allison for their discovery of cancer therapy by inhibition of negative immune regulation. This year’s Nobel Laureates have established an entirely new principle for cancer therapy by stimulating the intrinsic capability of our immune system to attack tumor cells.

James P. Allison examined a protein that is known to act as a brake on the immune system. He realized the potential of releasing the brake and as a result unleashing our immune cells to attack tumors. Next, he developed this notion into a brand new way to treat patients.

Alternatively, Tasuku Honjo found a protein on immune cells and so, after meticulous examination of its function, finally found that it also worked as a brake, but with a different mechanism of action. Therapies which are founded on his discovery have been proven to be hugely effective in the fight against cancer.

Allison and Honjo have exhibited how different strategies for inhibiting the brakes on the immune system can be utilized for the treatment of cancer. These groundbreaking findings constitute a landmark in the fight against cancer.

Below is a short video gathered using the 3D Cell Explorer which shows a cancer cell being killed by a T-cell.

About Nanolive SA

Nanolive SA are scientists, working for scientists.

Their belief is that each and every Biologist, Researcher and Physician should be able to explore and interact instantly with living cells without damaging them.

Nanolive want to support the study of how living cells and bacteria work, evolve and react, thus building a solid base for new drugs and therapies, in order to enable breakthrough researches.

This is the reason why they have developed the 3D Cell Explorer.


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Last updated: Mar 12, 2019 at 3:59 AM

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