The Cancer-Immunity Cycle - Image Gallery

Step 1 -- Cancer Cells Develop Antigens, or Neoantigens

Lymphoma cancer cell, scanning electron microscopy.


Cancer cells often have a number of changes in their genes that make them highly adaptable, or sneaky, if you will. Successful targeting of a malignancy often involves taking such adaptability into account. Sometimes a series battles rather than one decisive victory is necessary, and sometimes, multiple battles need to be fought simultaneously on different fronts.

The cancer-immunity cycle is at the crossroads of one of these battles, or fronts. It's a series of 7 steps that influences whether the immune response against the cancer cells is weak -- like a pebble hitting a truck -- or an all-out assault that is effective at actually killing the cancer cells.

Simplified Overview:

  • As cancer cells die, they release antigens, or substances that can be recognized by the immune system.
  • Antigens from the cancer cells are then taken up and presented on the cell surface of special immune cells so that other immune cells can “see” the antigens of interest.
  • This leads to the activation of T cells, which then travel via the blood vessels to reach the tumor, infiltrate it, recognize the cancer cells and kill them.

The 7 steps of the cycle are further explained in the image gallery.


Mutations in cancer cells cause the release of substances called “antigens” that show that cancer cells are different from normal cells. This allows the immune system to recognize them.

Step 1, Up Close

As you know, your immune system has the ability to recognize foreign invaders like bacteria and viruses. But did you know your immune system also detects what might be described as “shoddy or foreign construction?” That’s right – a veritable chunk of bricks and mortar that your body assesses and quickly deems “not my product, not of my construction, therefore foreign.”

Chunks may be bits of the cell wall from a dead bacterium, a piece of protein from a virus, or part of a capsule formed by bacteria, for instance; but foreign materials may also arise from within, as they do in cancer.

Cancer cells accumulate a number of genetic changes. Changes may result in differences from self -- that is, detectible differences in the cancer cells that the immune system can latch onto.

These parts of cancer cells that the immune system can recognize as foreign are called “neoantigens.” They arise from our own cells, gone amuck with caner -- rather than, say, an invading influenza virus.

Step 2 -- Special Immune Cells Process and Display Antigens

Larger antigen presenting cells capture, process and show antigens in context of special receptors to T-cells, small and purple.

Immune cells that specialize in identifying and capturing antigens process these bits of foreign material and take them to T cells, located in the lymph nodes.

Immunotherapy can boost immunity at this step and others. Antigen-presenting cells are a mixed group of immune cells that get involved in the cellular immune response by processing and presenting antigens for recognition by certain lymphocytes such as T cells. Some of the cells that can perform this function include dendritic cells, macrophages, Langerhans cells and B cells.

Step 3 -- T Cell Activation

T lymphocyte, artistic rendition. T cells become primed or activated when their receptors "see" antigen in the right context.

Activation of T cells. In this step, T cells become primed or activated by these foreign antigens, which begins the immune response against cancer cells.

After small fragments of foreign materials are transported to the surface of antigen presenting cells, this allows T cell to scan for foreign signals. T-cells interact with a large number of different cell types and can recognize a huge variety of invaders.

Step 4 -- Zeroing In On The Tumor

Activated T cells travel through the bloodstream to reach their targets.

Activated T cells then travel through blood vessels towards the location of the tumor.

A T cell that becomes activated in the lymphoid tissues can travel through the lymph system and enter the bloodstream by way of the thoracic duct. Once in the blood stream, a variety of factors come together to help activated t cells get to where they need to be. These factors may include changes in the T cells that occur during maturation as well as signs and signals in the blood vessels near the area of the tumor.

Step 5 -- Target Vicinity Reached, Commence Tumor Infiltration

T cells get to the location of the tumor and then crawl through the lining of the blood vessels.

T cells reach the cancer cells and infiltrate the tumor in order to attack it.

Once on-site, T cells are believed to get to their targets by way of a number of mechanisms. With inflammation affecting the tumor, blood vessels can dilate and become thinner and immune cells stick to the walls of the blood vessels. Cells that form the lining of the blood vessels are called endothelial cells. Immune cells crawl in between these endothelial cells to get to the tumor.

Step 6 -- Target Acquired

The smaller cell in the upper left is the T cell. It is approaching the cancer cell, which it will recognize as foreign.

T cells recognize cancer cells as foreign based on the antigens cancer cells released earlier in the cancer-immunity cycle.

T cells in tumors encounter not just the cancer cells, but oftentimes a whole cast of characters, including other immune cells. The CD8+ cytotoxic lymphocyte has been shown to interact with tumor cells through a special receptor. But other cells in the local environment -- the tumor microenvironment -- can play a big role in determining what kind of response the T cells are able to mount.

Step 7 -- Commence Target Destruction

Cytotoxic T cell in action, killing the cancer cell. Artistic rendition.

T cells destroy cancer cells by activating a series of steps that lead to cell death. At this step, immunotherapy can be used to inhibit certain inhibitors of cancer cell death.

Step 7 Up Close: The Dimmer Switch

T-cells, members of the immune system’s “army,” may be able to recognize neoantigens on cancer cells, but a powerful attack by T-cells on the malignant cells is still far from guaranteed; sometimes the tumor dials down the T-cell response to the cancer.

You may be familiar with those dimmer switches that let you set the mood lighting in dining rooms and such. Well, such a dimmer switch is technically a kind of rheostat, or a device that lets you vary the resistance in an electrical circuit without interrupting the circuit.

Sometimes there is a dimmer switch of sorts in the tumor microenvironment – the place where tumors grow and interact with other cells. This dimmer switch diminishes the immune system’s anti-cancer efforts; factors in the tumor microenvironment can act to restrain activated antitumor T cell immune response, acting as an immune rheostat or ‘‘immunostat,’’ according to a July 2013 article published in “Immunity."

The immune rheostat is not completely understood, however certain molecules that seem to be important in the immune system's interaction with cancer have been identified, including programmed death-ligand 1, or PD-L1, and programmed death-1, or PD-1.

Agents that inhibit parts of this dimmer switch represent one way of preventing cancer from disabling T cells in the tumor microenvironment.

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