Immunotherapy
For Lung Cancer

How is Immunotherapy for Lung Cancer Changing the Outlook for Patients?

Reviewed by:

Matthew Hellmann, MD
Memorial Sloan Kettering Cancer Center

Immunotherapy for lung cancer, alone or in combination with conventional treatments, can significantly improve outcomes for patients fighting lung cancer.

As the most common cancer worldwide, lung cancer impacts approximately 2.1 million people—and causes an estimated 1.7 million deaths—each year and is the leading cause of cancer-related deaths for both men and women. In the United States alone, there were an estimated 240,000 new lung cancer cases along with 130,000 deaths in 2023. Lung cancer claims more lives every year than do cancers of the breast, prostate, and colon combined.

Lung cancer is subdivided into two major types: 

  • Small cell lung cancer (SCLC) comprises approximately 10-15% of all known lung cancer cases.
  • Non-small cell lung cancer (NSCLC) comprises approximately 85-90% of all known lung cancers cases.
    • Adenocarcinoma arises from cells in the lung that secrete substances such as mucus (40% of lung cancers).
    • Squamous cell (epidermoid) carcinoma arises from the flat squamous cells that line the inside of the airways of the lung (25-30% of lung cancers). 
    • Large cell (undifferentiated) carcinoma typically arises from the epithelial cells that line the outer regions of the lung (10-15% of lung cancers).
  • Mesothelioma arises from a thin layer of tissue that covers many organs and most commonly occurs around the lungs.

When most lung cancer patients become symptomatic and are diagnosed, the disease has already advanced to late stage (at stage 3b/4 or higher). At these stages, surgery, chemotherapy, and radiation are only minimally effective. New treatments are needed for patients facing an advanced lung cancer diagnosis. Fortunately, immune-based cancer treatments are helping to improve chances of living longer for patients with lung cancer.

Lung Cancer Treatment Options

Until recently, conventional treatment options for lung cancer included surgery, chemotherapy, and radiation. Since the majority of lung cancer patients are diagnosed with advanced disease (stage 3b/4), these treatments are unlikely to result in complete cures, though they may significantly improve survival and provide symptom relief.

In 2015, the U.S. FDA approved the first immunotherapy to treat a subset of lung cancer patients. Immunotherapy is class of treatments that helps a person’s own immune system eliminate or control cancer. Recent clinical studies treating patients with immunotherapy, either alone or in combination with other treatments, have demonstrated significant patient improvement, resulting in FDA approval of several other immunotherapy options for more lung cancer patients, including approvals to treat patients with immunotherapy as a first-line therapy instead of conventional treatments.

Targeted Antibodies

  • Amivantamab (Rybrevant™): a bispecific antibody that targets EGFR and MET receptors on tumor cells; approved for subsets of patients with non–small cell lung cancer (NSCLC)
  • Bevacizumab (Avastin®): a monoclonal antibody that targets the VEGF/VEGFR pathway and inhibits tumor blood vessel growth; approved for subsets of patients with advanced non-small cell lung cancer (NSCLC), including as a first-line therapy
  • Necitumumab (Portrazza®): a monoclonal antibody that targets the EGFR pathway; approved for subsets of patients with advanced non-small cell lung cancer (NSCLC), including as a first-line therapy
  • Ramucirumab (Cyramza®): a monoclonal antibody that targets the VEGF/VEGFR2 pathway and inhibits tumor blood vessel growth; approved for subsets of patients with non-small cell lung cancer (NSCLC), including as a first-line therapy
  • Trastuzumab deruxtecan (Enhertu®): an antibody-drug conjugate that targets the HER2 pathway and delivers toxic drugs to tumors; approved for subsets of patients with advanced lung cancer

Immunomodulators

  • Atezolizumab (Tecentriq®): a checkpoint inhibitor that targets the PD-1/PD-L1 pathway; approved for patients with advanced non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), including as a first-line therapy in combination with chemotherapy.
  • Cemiplimab (Libtayo®): a checkpoint inhibitor that targets the PD-1/PD-L1 pathway; approved for a subset of patients with advanced non–small cell lung cancer (NSCLC) 
  • Dostarlimab (Jemperli): a checkpoint inhibitor that targets the PD-1/PD-L1 pathway; approved for subsets of patients with advanced lung cancer that has DNA mismatch repair deficiency (dMMR)
  • Durvalumab (Imfinzi®): a checkpoint inhibitor that targets the PD-1/PD-L1 pathway; approved for subsets of patients with lung cancer, including in combination with tremelimumab
  • Ipilimumab (Yervoy®): a checkpoint inhibitor that targets the CTLA-4 pathway; approved, in combination with nivolumab, as a first-line treatment, both with or without chemotherapy, for patients with advanced non-small cell lung cancer (NSCLC) and mesothelioma
  • Nivolumab (Opdivo®): a checkpoint inhibitor that targets the PD-1/PD-L1 pathway; approved for patients with advanced non-small cell lung cancer (NSCLC) and mesothelioma in combination with ipilimumab, with or without chemotherapy; also approved for NSCLC in the neoadjuvant (pre-surgical) setting in combination with chemotherapy
  • Pembrolizumab (Keytruda®): a checkpoint inhibitor that targets the PD-1/PD-L1 pathway; approved for patients with non-small cell lung cancer (NSCLC), including as a first-line therapy, an adjuvant (post-surgery) therapy, or in combination with chemotherapy
  • Tremelimumab (Imjudo®): a checkpoint inhibitor that targets the CTLA-4 pathway; approved in combination with durvalumab and chemotherapy for subsets of patients with metastatic lung cancer

These checkpoint immunotherapy approvals were landmark events for the treatment of lung cancer. With these immunotherapies, many advanced-stage lung cancer patients are starting to see long-lasting remissions and longer survival rates. Several immunotherapy agents are currently being tested in lung cancer clinical trials.

CRI’s Impact in Lung Cancer

Since its founding, the Cancer Research Institute (CRI) has dedicated numerous grants and fellowships to the research of immunotherapy for lung cancer. We continue to fund the science of immune-based therapies for lung cancer, supporting the best scientists working to advance the field of this promising treatment.

CRI-funded discoveries and breakthroughs, along with ongoing studies, include: 

See what lung cancer-specific research we’re currently funding. With your help, we can fund more research and revolutionize the way lung cancer is treated, forever—helping more people and saving more lives.

Related Links

Lung Cancer Statistics

1 in 4 Cancer-related deaths caused by lung cancer

#1 Leading cause of cancer deaths among both men and women

Approx. 80% Of lung cancer caused by cigarette smoking

2.1 Million newly diagnosed patients each year globally

Lung Cancer Clinical Trial Targets

Discover the different proteins, pathways, and platforms that scientists and physicians are pursuing to develop new cancer treatments. Use this information to consider your clinical trial options.

Targeted antibodies are proteins produced by the immune system that can be customized to target specific markers on cancer cells in order to disrupt cancerous activity, especially unrestrained growth. Antibody-drug conjugates (ADCs) are equipped with anti-cancer drugs that they can deliver to tumors. Bi-specific T cell-engaging antibodies (BiTEs) bind both cancer cells and T cells in order to help the immune system respond more quickly and effectively. Antibody targets under evaluation in lung cancer clinical trials include:

  • cMET: a growth-related pathway that is often abnormally activated in cancer
  • EGFR: a pathway that controls cell growth and is often mutated in cancer
  • HER2: a pathway that controls cell growth and is commonly overexpressed in cancer and associated with metastasis
  • Mesothelin: a protein that is commonly overexpressed in cancer and may aid metastasis
  • TROP2: a protein that is commonly overexpressed in cancer and appears to aid cancer cell self-renewal, proliferation, invasion, and survival
  • VEGF/VEGF-R: a pathway that can promote blood vessel formation in tumors

Cancer vaccines are designed to elicit an immune response against tumor-specific or tumor-associated antigens, encouraging the immune system to attack cancer cells bearing these antigens. Cancer vaccines can be made from a variety of components, including cells, proteins, DNA, viruses, bacteria, and small molecules. Cancer vaccine targets under evaluation in lung cancer clinical trials include:

  • EGFR: a pathway that controls cell growth and is often mutated in cancer
  • Mesothelin: a protein that is commonly overexpressed in cancer and may aid metastasis
  • MUC-1: a sugar-coated protein that is commonly overexpressed in cancer
  • NY-ESO-1: a protein that is normally produced only before birth, but is often abnormally expressed in cancer
  • Personalized neoantigens: these abnormal proteins arise from mutations and are expressed exclusively by tumor cells
  • Tumor-associated antigens (TAAs): proteins often expressed at abnormally high levels on tumor cells that can be used to target them; also found on normal cells at lower levels

Adoptive cell therapy takes a patient’s own immune cells, expands or otherwise modifies them, and then reintroduces them to the patient, where they can seek out and eliminate cancer cells. In CAR T cell therapy, T cells are modified and equipped with chimeric antigen receptors (CARs) that enable superior anti-cancer activity. Natural killer cells (NKs) and tumor infiltrating lymphocytes (TILs) can also be enhanced and reinfused in patients. Cell-based immunotherapy targets under evaluation in lung cancer clinical trials include:

  • MAGE antigens: the genes that produce these proteins are normally turned off in adult cells, but can become reactivated in cancer cells, flagging them as abnormal to the immune system
  • Mesothelin: a protein that is commonly overexpressed in cancer and may aid metastasis
  • NY-ESO-1: a protein that is normally produced only before birth, but is often abnormally expressed in cancer
  • ROR1: an enzyme that is normally produced only before birth, but is often abnormally expressed in cancer and may promote cancer cell migration as well as prevent cancer cell death

Immunomodulators manipulate the “brakes” and “gas pedals” of the immune system. Checkpoint inhibitors target molecules on immune cells to unleash new or enhance existing immune responses against cancer. Cytokines regulate immune cell maturation, growth, and responsiveness. Adjuvants can stimulate pathways to provide longer protection or produce more antibodies. Immunomodulator targets under evaluation in lung cancer clinical trials include:

  • CD40: activating this co-stimulatory pathway can kick start adaptive immune responses
  • CD73 or A2AR: blocking these pathways can help prevent the production of immunosuppressive adenosine
  • CD137 (also known as 4-1BB): activating this co-stimulatory pathway can help promote the growth, survival, and activity of cancer-fighting T cells
  • CSF1/CSF1R: blocking this pathway can help reprogram cancer-supporting macrophages
  • CTLA-4: blocking this pathway can help promote expansion and diversification of cancer-fighting T cells
  • GITR: activating this pathway can help prevent immunosuppression and increase the survival of cancer-fighting T cells
  • ICOS: activating this co-stimulatory pathway on T cells can help enhance immune responses against cancer
  • IDO: blocking this enzyme’s activity can help prevent cancer-fighting T cells from being suppressed
  • IL-2/IL-2R: activating this cytokine pathway can help promote the growth and expansion of cancer-fighting T cells
  • LAG3: blocking this pathway may be able to help prevent suppression of cancer-fighting T cells
  • OX40: activating this co-stimulatory pathway can help promote T cell survival after activation
  • PD-1/PD-L1: blocking this pathway can help prevent cancer-fighting T cells from becoming “exhausted” and can restore the activity of already exhausted T cells
  • Toll-like receptors (TLRs): activation of these innate immune receptors can help stimulate vaccine-like responses against tumors

Oncolytic virus therapy uses viruses that are often, but not always, modified in order to infect tumor cells and cause them to self-destruct. This can attract the attention of immune cells to eliminate the main tumor and potentially other tumors throughout the body. Viral platforms under evaluation in lung cancer clinical trials include:

  • Adenovirus: a family of common viruses that can cause a wide range of typically mild effects including sore throat, fatigue, and cold-like symptoms
  • Vaccinia virus: the virus that was used to help vaccinate against and eliminate smallpox; rarely causes illness in humans and is associated with a rash covering the body

Find an Immunotherapy Clinical Trial

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