Your doctor will analyze the cancer cells in a biopsy specimen or fluid taken from the lung or elsewhere to define the type of lung cancer, which will help guide treatment decisions.
Adenocarcinoma is the most common subtype diagnosed, especially in never smokers. It generally begins in the mucus-producing cells in the more distal (those that are farthest away) airways. Because it tends to grow more slowly than other types of lung cancer, adenocarcinoma is slightly more likely to be found before it spreads. Adenocarcinomas tend to develop in the peripheral lung and spread to distant sites more often than other types except for small cell lung cancer.
Squamous cell lung cancer (epidermoid carcinoma) is the second most common and starts in the early versions of squamous cells, the thin, flat cells that line the more central airways in the lungs. It most often develops in smokers and in the central lung. It spreads to distant sites less often than adenocarcinomas.
Large cell lung cancer can develop anywhere in the lungs and tends to grow and spread quickly. When it includes neuroendocrine features, it may behave and be treated like small cell lung cancer.
Adenocarcinoma and squamous cell and large cell lung cancers are sometimes collectively referred to as non-small cell lung cancer (NSCLC), which accounts for the majority of lung cancer diagnoses. Each type has distinct characteristics and responses to treatment, which makes it important for your doctor to determine the specific type.
Small cell lung cancer (SCLC), named for its appearance under a microscope, often starts in the central airways (bronchi) in the center of the chest. An aggressive form of lung cancer, it most often spreads to distant parts of the body before it is found. SCLC cells may secrete proteins that cause symptoms such as neurologic weakness or abnormalities in blood electrolytes.
WHAT IS THE IMMUNE SYSTEM?
To understand how your immune system can be used to fight 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 bacteria, cancer cells and other microscopic invaders.
Its first job is to distinguish between what is part of the body (self) and what is not (non-self). Once it determines that a cell is non-self, or foreign, to the body, it begins a series of reactions to identify, target and eliminate the non-self cells (see Figure 2, page 2).
The lymphatic system, which is made up of lymph nodes, the spleen, thymus, adenoids and tonsils, is a driving force in the immune system. Lymph, a clear fluid, collects and filters bacteria, viruses, toxins and chemicals known as antigens as it circulates 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.
Lymph contains lymphocytes, a type of white blood cell that attacks infectious agents. Lymphocytes begin in the bone marrow and develop from lymphoblasts (immature cells found in bone marrow). 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 it can recognize them and respond if they return.
T-cells also develop in the bone marrow and mature into four types: helper, killer, regulatory and memory T-cells. Each responds to non-self antigens in different ways.
HOW THE IMMUNE SYSTEM ELIMINATES CANCER
An immune response begins when B-cells and helper T-cells identify a non-self antigen and tell the rest of the immune system. The body then ramps up its production of T-cells to fight and destroy the antigen.
The immune system uses the 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 aren’t always effective. The immune system may have difficulty identifying cancer cells as non-self. It may still see them as 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.
Additionally, cancer cells 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 other immune cells. This allows the cancer to take control of certain parts of the process that the body uses to regulate the immune response. This means that 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 area. Immunotherapy offers the immune system reinforcements to keep up its fight.
IMMUNOTHERAPY: YOUR POTENTIAL TREATMENT PATH
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 (see Molecular Testing, page 7).
It’s important to note that immunotherapy is not effective for every person, even if it is approved for that person’s cancer type. Doctors and scientists are involved in clinical trials to learn why, as well as to improve
existing therapies and develop new ones.
Biomarker testing may be a requirement, particularly in clinical trials, because some types of immunotherapy are approved to treat cancers in people who have specific biomarkers. This helps doctors recommend immunotherapy only to patients who are most likely to respond. One test determines how many of your cancer cells express a protein called programmed death-ligand 1 (PD-L1). If there is a large amount of these proteins, immunotherapy alone may be used. If there are fewer, chemotherapy combined with immunotherapy may be used.
Depending on the cancer's type and stage and unique characteristics, such as previous treatments, age and general health, your doctor may select immunotherapy alone or combined with one of the following therapies.
- Surgery is the removal of the tumor and some surrounding normal tissue.
- Chemotherapy involves drugs to stop the growth of or directly kill cancer cells throughout the whole body. How it is given depends on the type and stage of the cancer.
- Radiation therapy uses high-energy X-rays or other types of radiation to kill cancer cells or stop them from growing.
- Targeted therapy involves drugs or other substances designed to attack cancer cells directly by targeting a specific abnormal gene or protein. Molecular (targeted) therapies are most often used in adenocarcinomas because molecular abnormalities are most common in this type of lung cancer.
- Clinical trials may involve immunotherapy and/or other treatment types.
Illustration: Figure 1 Anatomy of Lungs (filename: Overview Lung Anatomy Fig 1)
Illustration: Figure 2 Normal Immune Response (filename: Overview Normal Immune Response Fig 2)
SIDEBAR: GLOSSARY
These definitions may help you better understand the terms your health care team uses.
MMUNE SYSTEM
Antibody: A protein B-cells make in response to antigens (foreign substances such as bacteria, viruses and toxins).
Antigen: Any substance that triggers an immune response. Bacteria, viruses, toxins, abnormal proteins in cancer cells and chemicals are all antigens.
B-cell: A type of immune cell that makes antibodies and other proteins to mark specific foreign substances for other immune cells to destroy. A B-cell is a type of lymphocyte or white blood cell.
Immune cells: White blood cells in the immune system that help defend against cancer, infectious disease and other threats to the many cells and tissues in the body.
Immune checkpoint inhibitor: A type of immunotherapy that blocks certain proteins or receptors some immune cells make to turn off an immune response. In effect, these inhibitors “release the brakes” on the immune system so T-cells can destroy cancer cells unchecked.
Immune-related adverse events (irAEs): The immune system’s overreaction to immunotherapy. In rare cases, irAEs can rapidly become life-threatening without medical attention.
Lymphocyte: A type of immune cell (white blood cell) in lymph tissue and blood. The main types are B-lymphocytes (B-cells) and T-lymphocytes (T-cells), which both help the immune system fight cancer and infections.
PD-1 (programmed cell death-1): A receptor that binds with another protein (PD-L1) to help keep the body’s immune response in check by turning off immune responses.
Receptors (immune receptors): Surface molecules on immune cells that bind to the surfaces of other immune cells. This typically causes the cell to produce signals that help cells communicate and regulate specific functions in the immune system.
T-cells: White blood cells (immune cells) that play a significant role in the immune system’s fight against infection and disease. They are a type of lymphocyte that can directly kill cancer cells.
White blood cells: Made in the bone marrow and found in the blood, spleen and lymph tissue, they are part of the body’s immune system and help the body fight infection and other diseases.
GENERAL TERMS
Biomarker: Also known as a tumor marker or biological marker, this substance is produced by cancer cells or other cells of the body in response to cancer and may help guide treatment.
Distant: Used to describe cancer that has spread beyond the local or regional area.
In-situ: A group of abnormal cells found only in the place where they first formed in the body. These cells have not spread to distant sites.
Localized: Disease that is limited to a certain part of the body.
Regional: Describes the body area right around the tumor.
Tumor microenvironment: The area that surrounds and sustains a tumor. It is made up of normal cells, molecules and blood vessels.
HEALTH CARE TEAM
Case manager: Your personal advocate who collaborates with health care professionals and non-medical personnel to help overcome various financial, logistical and other common barriers to care.
Medical oncologist: Physician who treats cancer using medications.
Multidisciplinary medical team: A medical team made up of many people, each with a specialized role in your treatment plan. They will work closely together to ensure you receive the best care possible.
Patient navigator: A health care team member who may or may not be licensed (also may be called a lay navigator) who will help guide you through diagnosis and treatment.
Pulmonologist: Physician who specializes in the evaluation and treatment of lung problems.
Some definitions courtesy of the website of the National Cancer Institute (www.cancer.gov)