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Immunotherapy For Lung Cancer
Published on: August 14, 2024
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Introduction 

Your body has a biological network called the immune system that can fight bacteria, viruses, and even cancer cells when stimulated. Immunotherapy is a treatment procedure that uses your body’s immune system to help identify, fight, and kill cancer cells.1 Lung cancer is one of the leading causes of cancer-related death, with approximately 1.8 million deaths in 2020, and the second most commonly diagnosed cancer worldwide after breast cancer.2 

Immunotherapy for lung cancer has become a significant topic of research because it opens up another type of treatment option alongside conventional treatment (i.e. surgery, chemotherapy and radiation) for cancer patients. Keep reading to discover more about how immunotherapy has become an important treatment option - alone or combined with other treatments for lung cancer patients that can help prolong life and relieve symptoms.1,3 

Overview of lung cancer 

Lung cancer can be classified into two main types: non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), each with distinct characteristics and treatment approaches.

CHARACTERISTICNSCLCSCLC
Prevalence485% of patients 15% of patients 
Subtypes1. Adenocarcinoma (40%)
2. Squamous cell carcinoma (25-30%)
3. Large cell carcinoma (5-10%)

Rare subtypes:

4. Adenosquamous carcinoma
5. Sarcomatoid carcinoma5		1. Small cell carcinoma (oat cell cancer)
2. Combined small cell carcinoma6,7
Growth rateGenerally slower growth8
Spreads early on and has a high proliferative rate9
Greatest risk factor:Smoking6,10,11,12
Examples of other risk factors include: Old age - as with most cancers, second-hand smoke, asbestos exposure, alcohol use, family history of lung cancer, and exposure to toxic substances (i.e., polycyclic aromatic hydrocarbons, heavy metals, and radon gas)6,10,11,12
Treatment approachSurgery, radiation therapy, chemotherapy, immunotherapy, molecularly targeted therapy, laser therapy, photodynamic therapy, cryosurgery and electrocautery4,12Surgery, chemotherapy, radiation therapy, immunotherapy, laser therapy, endoscopic stent placement6
Prognosis Varied, depends on the subtype and stage11Poor prognosis due to aggressiveness9

Basic overview of the immune system

The immune system is your body’s system to fight against foreign materials, ‘germs’, that enter your body and make changes that could make you sick. The immune system has three essential roles: to fight against foreign germs; to identify and remove harmful substances from the environment; and to fight cells that cause changes and make you develop diseases - such as cancer.

If the immune system does not recognise the germ, it triggers processes that help store information about the germ and how to attack it. The next time the same germ enters, the immune system is prepared and responds faster to fight off the germs. The immune system consists of two subsystems called innate and adaptive immune systems.13,14

Innate and adaptive immune system

The innate system is the first line of defence mechanisms and barriers to prevent germs from entering the body (e.g., through the skin, digestive or respiratory system) to prevent the development of infection and eliminate germs.15

The adaptive system is the body’s way of learning and remembering how to deal with these germs. There are three crucial components in the adaptive system: T cells, B cells and antibodies.

ADAPTIVE SYSTEM COMPONENTS ROLE
T cellsActivate other immune cells, identify and destroy infected or abnormal cells, and form memory cells

T cells work in a key-lock type of mechanism whereby the T cells have detection sensors on their surface and attach to germs' surface - ‘antigens’
B cells Produce antibodies - the body produces its own weapons called ‘antibodies’ designed to target and specifically attack the germs encountered before
AntibodiesCirculate in your blood and fight off germs if they enter the bloodstream

Immune response to lung cancer

Cancer cells are the body’s cells that are transformed into cells that can cause disease. The immune system can monitor, recognise and eliminate these dangerous cells. However, cancer cells can dodge the immune system by appearing similar to healthy cells and blocking the activation of immune system cells that can kill the cancer cells.16

The immune system’s response to lung cancer encounters several challenges that complicate the body's ability to combat the disease effectively. For example, cancer cells escape surveillance by creating an environment that hinders the activation of immune system cells (e.g., T cells) required for immune response. Despite challenges, advancements in understanding the immune biology and mechanisms of lung cancer have paved the way for the emergence of immunotherapy as a viable approach to the management of the disease.16 

Checkpoint inhibitors — PD-1/PD-L1

Immunotherapy uses the body’s immune system to target and attack cancer cells, that is, it does not attack cancer cells directly. Checkpoint inhibitors are the most common type of immunotherapy used for lung cancer.16

PD-1 stands for programmed cell death protein 1 and PD-L1 stands for programmed cell death ligand 1. The mechanism of action of these checkpoint inhibitors is as follows: 

  • PD-L1, on the surface of tumour cells, interacts with PD-1 on the surface of T cells
  • This interaction stops the stimulation of the immune system
  • The recognition and killing of cancer cells by T cells are ‘put on hold’
  • This leads to cancer cells evading destruction by T cells

The treatment works when the inhibitors block the binding and interaction of PD-L1 and PD-1 and by enhancing the immune system's ability to recognise and attack lung cancer cells.

Ongoing immunotherapy research in lung cancer is being done in the following fields:16

Approved immunotherapies for lung cancer

Immunotherapy has emerged as one of the common options for treating lung cancer. Immunotherapy can be offered as first-line therapy, before or after other treatments, and when conventional treatment doesn't work, like in advanced lung cancer cases. Your doctor may recommend the following immunotherapy drugs based on your case.

Currently, there are four licensed immunotherapy drugs in the UK for lung cancer patients: 

Name of the drug (brand name)Type of inhibitor NSCLC cases that may be recommended immunotherapy:SCLC cases that may be recommended immunotherapy:
Pembrolizumab (Keytruda)PD-L1 -After surgery (stages 1B to 3A)
-Metastatic cancer AND no prior treatment 		-
Atezolizumab (Tecentriq)PD-L1 -After surgery (stages 2 to 3A)
-Metastatic cancer AND with other treatments (bevacizumab, carboplatin and paclitaxel)
-Metastatic cancer AND no prior treatment		Advanced AND combination treatment with chemotherapy 
Durvalumab (Imfinzi)PD-L1-After chemoradiotherapy AND stage 3 AND locally advanced cancer-
Nivolumab (Opdivo)PD-1 inhibitor-Before surgery AND cancer is removable
-Locally advanced OR metastatic squamous cases 		-

Side effects

Common side effects can include:

  • Fever
  • Feeling sick
  • Dryness
  • Itchiness
  • Breathlessness
  • Cough 
  • Loss of appetite
  • Fatigue
  • Headache

It is crucial to be aware of the potential side effects of taking the drugs. Side effects can range from mild to life-threatening, and you must contact a specialist to manage your side effects if you see the signs.

FAQs

How do you use immunotherapy drugs? 

Medication is administered intravenously, and delivered into the bloodstream through a tube inserted into a vein.

How successful is immunotherapy for lung cancer?

Immunotherapy can be successful for some lung cancer patients, especially those with specific biomarkers, but it doesn't work for everyone. It's often more effective in combination with other treatments or for certain types of lung cancer.

Does immunotherapy wipe out your immune system?

Immunotherapy doesn't wipe out your immune system; it boosts or directs it to fight cancer, though it can sometimes cause it to attack healthy cells too. Side effects vary but are generally managed by your healthcare team.

What are good signs immunotherapy is working?

Good signs include tumour shrinkage, stable disease, or feeling better overall, though doctors will monitor specific markers. Regular scans and blood tests help determine if the treatment is working.

Can you go into remission on immunotherapy?

Yes, some patients can go into remission on immunotherapy, but results vary depending on the individual and cancer type. Remission might last long-term, but ongoing monitoring is essential.

Summary 

  • Immunotherapy for lung cancer does not directly kill cancer cells but stimulates the immune system to recognise and kill cancer cells
  • Immunotherapy serves as a treatment choice for lung cancer, particularly in individuals dealing with advanced stages of the disease
  • Currently, only four immunotherapy drugs are approved for lung cancer
  • Side effects can range from mild to severe

References 

  1. Lahiri A, Maji A, Potdar PD, Singh N, Parikh P, Bisht B, et al. Lung cancer immunotherapy: progress, pitfalls, and promises. Mol Cancer [Internet]. 2023 Feb 21 [cited 2023 Dec 9];22:40. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9942077/
  2. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA A Cancer J Clinicians [Internet]. 2021 May [cited 2023 Dec 9];71(3):209–49. Available from: https://acsjournals.onlinelibrary.wiley.com/doi/10.3322/caac.21660
  3. Hirsch FR, Scagliotti GV, Mulshine JL, Kwon R, Curran WJ, Wu Y-L, et al. Lung cancer: current therapies and new targeted treatments. The Lancet [Internet]. 2017 [cited 2023 Dec 9]; 389(10066):299–311. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0140673616309588.
  4. Alduais Y, Zhang H, Fan F, Chen J, Chen B. Non-small cell lung cancer (Nsclc): A review of risk factors, diagnosis, and treatment. Medicine [Internet]. 2023 Feb 22 [cited 2023 Dec 9];102(8):e32899. Available from: https://journals.lww.com/md-journal/fulltext/2023/02220/non_small_cell_lung_cancer__nsclc___a_review_of.2.aspxm 
  5. Zheng M. Classification and Pathology of Lung Cancer. Surgical Oncology Clinics of North America [Internet]. 2016 [cited 2023 Dec 9]; 25(3):447–68. Available from: https://linkinghub.elsevier.com/retrieve/pii/S1055320716000053.
  6. Morabito A, Carillio G, Daniele G, Piccirillo MC, Montanino A, Costanzo R, et al. Treatment of small cell lung cancer. Critical Reviews in Oncology/Hematology [Internet]. 2014 [cited 2023 Dec 9]; 91(3):257–70. Available from: https://www.sciencedirect.com/science/article/pii/S1040842814000523.
  7. Basumallik N, Agarwal M. Small cell lung cancer. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 [cited 2023 Dec 9]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK482458/
  8. Zappa C, Mousa SA. Non-small cell lung cancer: current treatment and future advances. Transl Lung Cancer Res [Internet]. 2016 Jun [cited 2023 Dec 9];5(3):288–300. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4931124/ 
  9. Rudin CM, Brambilla E, Faivre-Finn C, Sage J. Small-cell lung cancer. Nat Rev Dis Primers [Internet]. 2021 Jan 14 [cited 2023 Dec 9];7(1):3. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8177722/ 
  10. Alexander M, Kim SY, Cheng H. Update 2020: management of non-small cell lung cancer. Lung [Internet]. 2020 Dec 1 [cited 2023 Dec 9];198(6):897–907. Available from: https://doi.org/10.1007/s00408-020-00407-5 
  11. Clark SB, Alsubait S. Non–small cell lung cancer. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 [cited 2023 Dec 9]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK562307/
  12. Herbst RS, Morgensztern D, Boshoff C. The biology and management of non-small cell lung cancer. Nature [Internet]. 2018 [cited 2023 Dec 9]; 553(7689):446–54. Available from: https://www.nature.com/articles/nature25183.
  13. How does the immune system work? In: InformedHealth.org [Internet] [Internet]. Institute for Quality and Efficiency in Health Care (IQWiG); 2020 [cited 2023 Dec 12]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK279364/
  14. Aristizábal B, González Á. Innate immune system. In: Autoimmunity: From Bench to Bedside [Internet] [Internet]. El Rosario University Press; 2013 [cited 2023 Dec 12]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK459455/ 
  15. The innate and adaptive immune systems. In: InformedHealth.org [Internet] [Internet]. Institute for Quality and Efficiency in Health Care (IQWiG); 2020 [cited 2023 Dec 12]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK279396/
  16. Saab S, Zalzale H, Rahal Z, Khalifeh Y, Sinjab A, Kadara H. Insights into lung cancer immune-based biology, prevention, and treatment. Frontiers in Immunology [Internet]. 2020 [cited 2023 Dec 12];11. Available from: https://www.frontiersin.org/articles/10.3389/fimmu.2020.0015
  17. Domagala-Kulawik J, Osinska I, Hoser G. Mechanisms of immune response regulation in lung cancer. Transl Lung Cancer Res [Internet]. 2014 Feb [cited 2023 Dec 12];3(1):15–22. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4367608/
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Nithursha Nagendrabalan

Master of Sciences in Cancer, University College London, England

I possess a solid academic background in biomedical sciences and cancer research. Encountering complex information through my educational journey has emphasised the vital need to render knowledge accessible to all. With my extensive knowledge and recognition of the significance of making science understandable, I am committed to translating complex scientific concepts into accessible articles.

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