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The power of observation

In 1665, Robert Hooke peered through a microscope — a relatively novel tool for biologists — and discovered the cell, changing our fundamental understanding of life. Today, microscopy is revealing how immune cells kill tumor cells and how cancer evades our normal defenses. Unraveling these complex relationships has revolutionized cancer care through the development of treatments like immunotherapies, which boost the immune system’s ability to fight cancer. But immunotherapies currently only work for a fraction of people with cancer, and researchers are investigating how to widen the circle of people who can benefit.

Take a journey with us and see what our researchers see through sophisticated microscopes as they carefully observe cellular activity and reveal how the immune system interacts with cancer.

An Immune Cell Engages Its Target

Killer T cells (orange) are immune cells that search the body for infected or abnormal cells, including cancer cells, and destroy them. In this video, the T cell is seen attached to a blue cancer cell. The fiery protrusions in the T cell are formed by the actin cytoskeleton — protein fibers inside the cell that gives it its shape and allows it to move through the body. This video shows that killer T cells strongly stick to cancer cells and that their cytoskeleton changes dramatically when they recognize a cancer cell. Now that the T cell has made contact, its next job is to kill the cancer cell.

An Immune Cell Eliminates Its Target

Here, a T cell (purple) is shown interacting with an ovarian cancer cell (teal). The T cell secretes toxins (red waves), which trigger the cell death response in the cancer cell, causing it to shrivel up and die. Although the video compresses about 75 minutes of activity, it’s important to note that it takes the T cell only 10 minutes to kill the cancer cell after recognizing it. This video demonstrates the potency and efficiency of our immune defenses against cancer. The goal of cancer immunotherapy is to harness this power to fight tumors more effectively. 

A Multi-Cell Attack

Here, you see a T cell (purple) coming in from the left and secreting its toxins (red wave), but the cancer cell (teal) survives. Then you see another T cell come from the top and deliver the second hit necessary to kill the cancer cell. It takes a certain amount of toxin to kill the cancer cell, and it may require multiple T cells cooperating to get the job done.

Using advanced microscopy techniques, researchers at Genentech discovered that cancer cells can repair their membranes after T cells poke holes in them, which prevents a lethal dose of toxin from entering and killing the cancer cells. Inhibiting this repair mechanism made T cells more effective at killing cancer cells in the lab, suggesting potential avenues for developing new immunotherapies. The study was led by Alex Ritter, PhD, a former Genentech postdoctoral researcher, and Ira Mellman, PhD, Vice President of Cancer Immunology at Genentech.

Visual observation has been the foundation of discovery — from evolution, to astronomy, to virology — since the beginning of scientific inquiry. Cancer biology is no exception, and for those studying the interactions between immune and tumor cells, the microscope remains a powerful tool. As microscopy technologies and techniques continue to evolve, so will our understanding of life, disease, and new ways to restore health.

To learn more about Genentech’s groundbreaking research, visit https://www.gene.com/topics/behind-the-science