Cancer Immunotherapy


Cancer develops when genes begin to change within the structure of normal cells. These cells – now called cancer cells – grow and push against normal cells. Sometimes they form tumors (or masses); other times, as in the case of most hematologic (blood) cancers, they don’t. Hematologic cancers affect the way blood cells are developed and the way they function.

Lymphoma starts in the lymphatic system and affects lymphocytes, which are part of the immune system. It develops when normal lymphocytes transform into abnormal, cancerous cells that reproduce uncontrollably. As they multiply, they collect in the lymph nodes, bone marrow (the spongy center of bones where blood cells are made), spleen, tonsils or other organs, where they can form tumors. These cells eventually begin to outnumber normal cells, which can cause the lymph nodes, spleen or other organs to enlarge.

Sometimes, lymphoma begins outside the lymphatic system, such as in the mediastinum (the area in the chest behind the breastbone), the central nervous system (brain and spinal cord) or on the skin.

To fully understand lymphoma, it helps to have a general knowledge of the lymphatic system. The lymphatic system is a network of tissues and vessels that carry fluid, called lymph, throughout the body. Lymph contains lymphocytes, a type of white blood cells.

The lymphatic system is made up of lymph nodes, as well as the spleen, thymus, adenoids and tonsils. Lymph nodes are located throughout the body, with larger concentrations near the abdomen, groin, pelvis, underarms and neck.

The main types of lymphocytes that can develop into lymphomas are B-lymphocytes (B-cells) and T-lymphocytes (T-cells).

  • B-cells produce protein antibodies that attach to infectious organisms, such as bacteria and viruses, marking them for destruction.
  • T-cells attack infectious organisms directly and can identify and attack body cells infected with a virus or altered by cancer. They also play a part in controlling the immune system.

Both B-cells and T-cells can transform into lymphoma cells. In the United States, B-cell lymphomas are much more common than T-cell lymphomas.

More About Lymphoma

Lymphoma can be classified as Hodgkin lymphoma (HL) or non-Hodgkin lymphoma (NHL).

NHL is much more common than HL and can be classified as indolent (slow growing) or aggressive (rapidly growing). NHL has more than 60 subtypes, and they vary in microscopic appearance and molecular features. They differ in how they affect the body and how they are treated. They also grow and spread at different rates.

If the initial treatment plan does not result in complete remission of your lymphoma, the disease is considered refractory. Immunotherapy is available to treat some types of refractory lymphomas. Different chemotherapy agents or targeted therapy drugs may be additional treatment options.

Relapsed lymphoma occurs when the disease comes back after successful treatment. A relapse can happen weeks, months or even years after initial treatment has ended. Treatments often reduce the amount of cancer cells, but some can remain undetected and continue to grow. Keep your follow-up appointments because finding any recurrence early is important. Your doctor will ask questions about any ongoing symptoms you may be having, especially those related to recurrence and long-term side effects.

Hodgkin lymphoma (HL), formerly known as Hodgkin disease, typically starts in the lymph nodes in the chest, neck or underarm and may spread to other lymph nodes or to other organs, such as the liver or lungs.

HL is classified as classical or nodular lymphocyte-predominant. The majority of HL cases are classical HL. The cancer cells found in classical HL are Reed-Sternberg cells, which are large, abnormal B-cell lymphocytes. Classical HL has four main subtypes:

  1. Nodular sclerosis HL is the most common. It occurs most often in the lymph nodes in the mediastinum (central part of the chest) or neck.
  2. Mixed cellularity HL is the second most common.
  3. Lymphocyte-rich HL is less common than the first two.
  4. Lymphocyte-depleted HL is the rarest. It is usually found in lymph nodes in the abdomen and also the spleen, liver and bone marrow. It is more aggressive than other types of HL.

Nodular lymphocyte-predominant HL accounts for the rest of the HL diagnoses. This type of lymphoma has large cells that are variants of Reed-Sternberg cells. Nodular lymphocyte-predominant HL is more similar to indolent B-cell NHL than classical HL and generally grows more slowly than classical HL. It usually begins in lymph nodes in the neck and under the arm.

Non-Hodgkin lymphoma (NHL) is one of the more common cancers after solid tumors in the United States. It starts in the lymphatic system, most often in the lymph nodes, liver, spleen or bone marrow, and it can involve the stomach, intestines, skin, thyroid, brain or any other part of the body where lymphatic tissue is found.

NHL is classified as indolent (slow growing) or aggressive (rapidly growing). Because more than 60 different subtypes of NHL exist, it can be difficult to classify. Determining the subtype is important because treatment will vary. Not all treatments will be effective for each subtype. Although the various types of NHL share some common features, they differ in their microscopic appearance, molecular features, growth patterns and effects on the body as well as treatment options.

Overall, the most common form of NHL is diffuse large B-cell lymphoma (DLBCL), which accounts for approximately 30 percent of all newly diagnosed cases of NHL. It is aggressive. The second most common type of lymphoma is follicular lymphoma. This type of lymphoma is indolent. Another indolent lymphoma is marginal zone lymphoma, which begins in the B-lymphocytes.

Most NHL subtypes affect the blood; however, another involves the skin. Cutaneous T-cell lymphoma (CTCL) is typically indolent but can sometimes be aggressive. Two subtypes of CTCL are mycosis fungoides and Sézary syndrome, which often appear as rashes, bumps or scaly patches on the skin.

Immunotherapy for Lymphoma

Various types of immunotherapy are approved to treat certain lymphoma diagnoses, bringing hope to many by offering the possibility of long-term remission.

Adoptive cellular therapy (T-cell therapy) in the form of chimeric antigen receptor (CAR T-cell) therapy is approved to treat several types of lymphoma, including patients up to age 25 years old in some instances (see CAR T-cell Therapy). Clinical trials continue to explore CAR T-cell therapies alone and in combination with other drugs for additional types of lymphoma and other cancers.

Cytokines are one of the first immunotherapy strategies approved for some lymphomas. Although they are not as widely used as they once were, they are still an option for treating certain types of lymphoma.

Immune checkpoint inhibitors may be used to treat classical HL that has relapsed or progressed after an autologous stem cell transplant or primary mediastinal B-cell lymphoma.

Monoclonal antibodies (mAbs), including naked mAbs, conjugated mAbs and bispecific mAbs, are widely used to treat many types of lymphoma. Some are combined with a radioactive substance in a type of immunotherapy called radioimmunotherapy.

Photopheresis, a type of immunotherapy first introduced in the 1980s, is used to treat cutaneous T-cell lymphoma (CTCL), a rare type of NHL, and other blood disorders.