Skin Cancers and the Immune System


Immunotherapy has revolutionized the treatment of certain types of melanoma and other skin cancers. Uniquely different from other types of cancer treatment, it uses the body’s own immune system to recognize and attack cancer cells that have been hiding and targets them for destruction. This ability to harness the power of the immune system is making it increasingly possible for many people with these diagnoses to live longer, better-quality lives. Understanding immunotherapy and its impact are important especially for newly-diagnosed patients. As the world’s leading member-driven organization specifically dedicated to improving cancer patient outcomes by advancing the science and application of cancer immunotherapy, the Society for Immunotherapy of Cancer (SITC) provides resources for patients to learn more about immunotherapy, its research and how it is improving outcomes for many cancer types.

Even with treatment advances, receiving a cancer diagnosis can feel overwhelming. The first step toward understanding all the new information you’ll hear is to know the specific type and stage of your diagnosis. This guide explains melanoma and other skin cancers, the immune system, immunotherapy and ways to help manage your treatment and follow-up care.


To understand how your immune system can be used to treat cancer, it’s helpful to know it’s a complex network of cells, molecules, organs and lymph tissues working together to defend the body against germs, microscopic invaders and even cancer cells.

The first job of the immune system is to distinguish between what is part of the body (self) and what is not part of the body (non-self or foreign). Viruses are one type of germ that can infect humans as they enter the normal cells of the body. The immune system has developed sophisticated ways to determine if a cell is normal or may contain a virus, or is abnormal for other reasons, such as injury or cancer. Once the immune system determines that a cell is not normal (or foreign to the body), it begins a series of reactions to identify, target and eliminate the abnormal cell. This process represents a way to protect against injury and foreign substances, such as germs. When you scrape your elbow, for example, the skin’s protective barrier is broken, and harmful non-self substances can easily enter the body.

The lymphatic system, which is made up of the spleen, thymus, adenoids, tonsils and lymph nodes, is a driving force in the immune system. Lymph, a clear fluid, is circulated throughout the body through the lymph nodes. It collects and filters bacteria, viruses, toxins and chemicals, which are circulating in the lymphatic system and bloodstream. Lymph nodes are located throughout the body, with large concentrations near the chest, abdomen, groin, pelvis, underarms and neck. The immune system recognizes abnormal cells or germs by “seeing” specific proteins or other molecules that are called antigens.

Lymph contains lymphocytes, a type of white blood cell that attacks infectious agents. The two main types of lymphocytes are B-lymphocytes (B-cells) and T-lymphocytes (T-cells).

B-cells develop in the bone marrow and mature into either plasma cells or memory cells. Plasma cells make antibodies to fight germs and infection. Memory B-cells help the immune system remember which antigens attacked the body so they can recognize them and respond if they return.

T-cells also develop in the bone marrow and mature into four cell types: helper, killer, regulatory and memory T-cells. Each responds to non-self antigens in different ways.


Each part of the immune system plays a role in defending the body. But, like any good team, these parts must be able to alert each other and communicate messages so the system can respond quickly to threats. Most cells communicate by sending chemical signals.

The surface of a cell is not completely round and smooth. It is covered with receptors and proteins, which work like puzzle pieces. Proteins have “tabs” that stick out, and receptors have “spaces” that curve inward. When the puzzle pieces fit together (known as binding), chemical signals and information are exchanged in a biochemical reaction. Cells also contain various proteins, sugars, fats and other molecules that stick out of their surfaces. These components contain information that is shared between cells.

An immune response typically begins when B-cells and helper T-cells identify a threat (non-self antigen) and tell the rest of the immune system. The body then ramps up its production of T-cells to fight. Killer T-cells are sent to destroy cells that contain the non-self antigens. Regulatory T-cells are sent to slow the immune system down once the cells that contain non-self antigens have been eliminated, to prevent the T-cells from attacking healthy parts of the body. T-cells then return to normal levels.

The immune system uses this same process to recognize and eliminate cancer, but the process is more complicated. Cancer cells are created by the body, so the normal ways to find and fight invading cells from outside the body aren’t always effective. The immune system may have difficulty identifying cancer cells as non-self. It may still see them as a normal part of the body and not coordinate an attack. If the body can’t tell the difference between tumor cells and normal cells, the tumor cells may be able to “hide” from the immune system.

Cancer cells are smart. Over time, they can change and use multiple methods to escape or confuse the immune system. One way is to produce proteins on their surface to hide from the immune system, like camouflage. Another is to create their own messengers (cytokines), which means that the cancer cells can communicate and confuse the immune cells. That allows the cancer to take control of certain parts of the process that the body uses to regulate the immune response. So, even if the immune system recognizes the cancer, it may not be able to successfully start or maintain an attack long enough to kill the cancer cells.

The longer the cancer cells face a weakened immune response, the more they’re able to adapt, and the easier it is for them to manipulate immune cells inside the tumor’s location, sometimes called the tumor microenvironment.

Immunotherapy offers the immune system reinforcements to keep up its fight, whether that is by taking the brakes off the system, boosting it with modified T-cells or combining it with chemotherapy or radiation therapy.


Some of the first types of immunotherapy approved by the U.S. Food and Drug Administration (FDA) for treating cancer were for melanoma. These approvals offered hope and durable responses to many who had Stage III and IV diagnoses, which had a poor prognosis, were difficult to treat and often spread quickly. Since then, the FDA has approved more immunotherapy drugs for both melanoma and other skin cancers, including cutaneous squamous cell and Merkel cell skin cancers. These drugs are considered breakthrough therapies that are offering a new way of treating these types of cancer.

Today, many immunotherapy options are available for people with melanoma and other skin cancers. These include cytokines, immune checkpoint inhibitors, immunomodulators and oncolytic virus therapy, which all work on different aspects of the immune system.

You may be a candidate for immunotherapy if you meet certain criteria. If you have a pre-existing autoimmune disorder, be sure to discuss it with your doctor. Immunotherapy is not effective for every person, even if it is approved for that person’s cancer type. Scientists are studying patient responses to immunotherapy to find out why. Researchers are also investigating other methods for using the immune system to fight cancer to improve the effectiveness of this treatment.

  • Has immunotherapy successfully treated my type of melanoma/skin cancer?
  • Am I a good candidate to receive immunotherapy?


Staging helps your medical team develop a personalized treatment plan based on the extent of disease and how far it has progressed.

The TNM classification system developed by the American Joint Committee on Cancer (AJCC) is used to stage melanoma and other skin cancers. The T category specifies the primary tumor’s size and location. The N category indicates whether lymph nodes show evidence of cancer cells. The location of these lymph nodes is important because it shows how far the disease has spread. The M category describes distant metastasis (spread) to other parts of the body, if any.