Understanding Cancer Immunotherapy: How It Works, Types and What to Expect
- Dr. Ryan Heals, Pharm.D.
- 22 hours ago
- 7 min read
Introduction of Understanding Cancer Immunotherapy
Cancer immunotherapy has transformed oncology more profoundly in the past two decades than any development since chemotherapy. Patients with metastatic melanoma — a cancer that was almost universally fatal just fifteen years ago — are now achieving long-term remissions. Lung cancer patients with specific molecular profiles are living years longer than was previously possible. Childhood leukaemia patients who had exhausted all other options are achieving complete remissions with a single infusion.
These are not isolated anecdotes. They are the outcomes of rigorous clinical trials that have led to over 80 FDA-approved immunotherapy treatments, with hundreds more currently in development.
This article explains what cancer immunotherapy is, how the immune system normally responds to cancer, why it often fails, and how the different types of immunotherapy correct those failures. It is an educational overview intended to help patients and their families understand the science behind treatments they may encounter or discuss with their oncology team.
The Immune System and Cancer: A Complex Relationship
To understand immunotherapy, it helps to first understand how the immune system relates to cancer in the absence of treatment.
The immune system is capable of recognising and destroying cancer cells. T-cells — the immune system's primary attack cells — can identify abnormal proteins on the surface of cancer cells (called neoantigens or tumour-associated antigens) and mount an attack. This process is called immune surveillance, and it is thought to prevent many potential cancers from ever developing into clinically detectable disease.
But cancer cells are evolutionarily adaptive. Over time, tumours develop strategies to evade immune destruction:
Downregulating antigen presentation:
Cancer cells reduce or eliminate the surface proteins that T-cells use to identify them as abnormal, essentially making themselves invisible to immune surveillance.
Activating immune checkpoints:
The immune system has built-in braking mechanisms — called immune checkpoints — designed to prevent it from attacking the body's own healthy tissues (autoimmunity). Cancer cells exploit these brakes by expressing proteins that tell T-cells to stand down. PD-L1, expressed on the surface of many tumour cells, binds to the PD-1 receptor on T-cells and suppresses their activity.
Creating an immunosuppressive tumour microenvironment:
Tumours recruit regulatory T-cells and other immunosuppressive cells that dampen the immune response within the tumour itself.
Outpacing immune control:
Rapidly dividing cancer cells can outgrow the immune response even when it is partially functioning.
Immunotherapy works by intervening at these points of failure — either removing the brakes on T-cells, directly engineering immune cells to recognise cancer, or providing the immune system with better tools to identify and attack tumour cells.
Type 1: Immune Checkpoint Inhibitors
Checkpoint inhibitors are currently the most widely used and most clinically impactful form of cancer immunotherapy. They have revolutionised treatment in melanoma, lung cancer, bladder cancer, kidney cancer, head and neck cancer, and many other tumour types.
How they work:
The most important immune checkpoints in cancer are:
PD-1/PD-L1 axis
PD-1 is a receptor on T-cells; PD-L1 is its ligand expressed on tumour cells. When PD-L1 binds PD-1, it tells the T-cell to deactivate. Many tumours exploit this to suppress T-cell attack.
CTLA-4
Another inhibitory receptor on T-cells. It competes with an activating receptor (CD28) for the same binding partner, suppressing T-cell activation.
Checkpoint inhibitor drugs are monoclonal antibodies that block these interactions:
PD-1 inhibitors:
Pembrolizumab (Keytruda), Nivolumab (Opdivo)
PD-L1 inhibitors:
Atezolizumab (Tecentriq), Durvalumab (Imfinzi)
CTLA-4 inhibitors:
Ipilimumab (Yervoy)
By blocking these checkpoints, the drugs release the brake on T-cells — allowing them to recognise and attack cancer cells that had previously evaded immune destruction.
Clinical impact:
The approval of ipilimumab for metastatic melanoma in 2011 was a watershed moment. Prior to this, median survival for metastatic melanoma was less than a year. Long-term follow-up data now shows that approximately 20% of patients treated with ipilimumab achieve durable long-term remission — potentially cured. Combination checkpoint blockade (PD-1 + CTLA-4 inhibitors) has improved these numbers further.
Side effects:
Because checkpoint inhibitors broadly activate the immune system, they can cause immune-related adverse events — the immune system attacking healthy tissues. These can affect any organ but most commonly cause colitis, hepatitis, pneumonitis, endocrinopathies (thyroid, adrenal, pituitary), and skin reactions. Management involves immunosuppression with corticosteroids and, in severe cases, stopping treatment.
Type 2: CAR-T Cell Therapy
Chimeric Antigen Receptor T-cell (CAR-T) therapy represents one of the most technically remarkable achievements in modern medicine. It involves genetically engineering a patient's own immune cells to become precision cancer-killing machines.
How it works:
Step 1.
T-cells are collected from the patient's blood through a process called leukapheresis
Step 2.
In the laboratory, the T-cells are genetically modified to express a Chimeric Antigen Receptor (CAR) on their surface
Step 3.
The CAR is engineered to recognise a specific protein on the surface of the patient's cancer cells
Step 4.
The modified CAR-T cells are expanded into hundreds of millions of cells in the laboratory
Step 5.
They are infused back into the patient, where they seek out and destroy cancer cells bearing the target protein
Step 6.
CAR-T cells can persist in the body for years, providing ongoing surveillance against cancer recurrence
Current approvals:
CAR-T therapies are currently approved for:
- B-cell acute lymphoblastic leukaemia (ALL) in children and young adults
- Diffuse large B-cell lymphoma
- Follicular lymphoma
- Multiple myeloma
- Mantle cell lymphoma
Outcomes:
In B-cell ALL, CAR-T therapy achieves complete remission rates of 70–90% in patients who had failed multiple prior treatments — some achieving what appears to be long-term cure.
Challenges and side effects:
CAR-T therapy can cause cytokine release syndrome (CRS) — a potentially life-threatening systemic inflammatory reaction as CAR-T cells massively activate and release inflammatory cytokines. Neurotoxicity (immune effector cell-associated neurotoxicity syndrome, ICANS) is another serious potential complication. CAR-T therapy currently requires specialist centres and is enormously expensive. Research is focused on making it more accessible, less toxic, and applicable to solid tumours — where it has so far been less effective.
Type 3: Cancer Vaccines
Cancer vaccines represent a fundamentally different concept from traditional vaccines — they are generally therapeutic rather than preventive, designed to treat existing cancer rather than prevent infection.
Tumour-specific (neoantigen) vaccines:
Next-generation sequencing can identify the unique mutations in an individual patient's tumour that create abnormal proteins (neoantigens) not found in normal cells. Personalised cancer vaccines present these neoantigens to the immune system, training it to recognise and attack cells carrying those specific abnormalities. These are currently in clinical trials across multiple cancer types and represent one of the most promising frontiers in oncology.
Approved therapeutic cancer vaccine:
Sipuleucel-T (Provenge) is the first FDA-approved therapeutic cancer vaccine, used for metastatic castration-resistant prostate cancer. It works by activating a patient's own immune cells against a prostate cancer antigen.
Preventive cancer vaccines:
Some vaccines do prevent cancer by preventing the infections that cause it:
HPV vaccines (Gardasil, Cervarix) prevent infection with cancer-causing strains of human papillomavirus, preventing cervical cancer, some oral cancers, and others
Hepatitis B vaccine prevents hepatitis B infection, which is a major cause of hepatocellular (liver) cancer
Type 4: Monoclonal Antibodies
Monoclonal antibodies (mAbs) are laboratory-made proteins that target specific antigens on cancer cells. They are among the most widely used cancer treatments today.
They work through several mechanisms:
Directly blocking tumour growth signals
e.g. Trastuzumab (Herceptin) targets HER2 receptors on breast cancer cells that drive tumour growth
Flagging cancer cells for immune destruction
the antibody attached to the cancer cell acts as a flag that natural killer cells and macrophages use to identify and destroy the cell
Delivering toxins or radioactive particles
antibody-drug conjugates (ADCs) use antibodies to deliver chemotherapy or radioactive payloads precisely to cancer cells
Blocking angiogenesis
Bevacizumab (Avastin) targets VEGF, blocking the formation of new blood vessels that tumours require to grow
Type 5: Cytokines and Adoptive Cell Transfer
Cytokines:
High-dose Interleukin-2 (IL-2) was one of the earliest immunotherapies, approved in the 1990s for melanoma and kidney cancer. It dramatically activates the immune system but causes severe toxicity. It has largely been superseded by better-tolerated checkpoint inhibitors.
Adoptive cell transfer (tumour-infiltrating lymphocytes, TIL therapy):
A newer approach in which T-cells that have naturally infiltrated the tumour (and therefore already recognise cancer antigens) are extracted, massively expanded in the laboratory, and reinfused. Lifileucel (Amtagvi) became the first approved TIL therapy in 2024 for advanced melanoma.
Who Responds to Immunotherapy — and Who Doesn't?
Not all patients or all cancers respond equally to immunotherapy. Key predictors of response include:
Tumour mutational burden (TMB):
Tumours with more mutations generate more neoantigens — more flags for the immune system to recognise. High-TMB tumours generally respond better to checkpoint inhibitors.
PD-L1 expression:
Higher PD-L1 expression on tumour cells often predicts better response to PD-1/PD-L1 inhibitors — though this is not a perfect predictor.
Microsatellite instability (MSI-H):
MSI-H tumours — which have defects in DNA mismatch repair — have high mutation rates and respond very well to checkpoint inhibitors regardless of tumour type. Pembrolizumab is approved for any MSI-H solid tumour.
Cancer type:
Some cancers are intrinsically more immunogenic (melanoma, lung cancer, kidney cancer) while others are more immunologically "cold" (pancreatic cancer, glioblastoma) and have responded less well to current immunotherapy approaches.
The Future of Immunotherapy
The field is evolving rapidly. Current research frontiers include:
Next-generation CAR-T
allogeneic (off-the-shelf) CAR-T from healthy donors, reducing cost and increasing accessibility
CAR-T for solid tumours
overcoming the immunosuppressive tumour microenvironment that has limited CAR-T efficacy outside blood cancers
Personalised neoantigen vaccines
combined with checkpoint inhibitors
Bispecific antibodies
antibodies that simultaneously bind a cancer antigen and a T-cell, physically bringing them together
Combinations
combining checkpoint inhibitors with chemotherapy, radiotherapy, targeted therapy, and other immunotherapy approaches
Frequently Asked Questions
What is the difference between immunotherapy and chemotherapy?
Chemotherapy directly kills rapidly dividing cells — including cancer cells, but also healthy cells like hair follicles, gut lining, and bone marrow, causing the well-known side effects. Immunotherapy works by activating or re-activating the immune system to find and destroy cancer cells. It does not directly kill cells but enables the immune system to do so. Side effects are different — immune-related rather than cytotoxic.
Does immunotherapy work for all cancers?
No. Immunotherapy has transformed treatment in melanoma, lung cancer, kidney cancer, bladder cancer, and several blood cancers. It is less effective in some others such as pancreatic cancer and glioblastoma. Research is actively working to extend its benefits to currently less responsive tumour types.
What are the side effects of immunotherapy?
The most significant side effects of checkpoint inhibitors are immune-related adverse events — the immune system attacking healthy tissues. Common targets include the bowel (colitis), liver (hepatitis), lungs (pneumonitis), and endocrine glands (thyroid, adrenal, pituitary). CAR-T therapy can cause cytokine release syndrome and neurotoxicity. Side effects vary significantly between individuals and treatment types.
How long does immunotherapy treatment last?
Duration varies by cancer type and treatment. Some patients receive a fixed number of cycles. Others continue as long as the treatment is working. Some achieve durable remissions and stop treatment. Your oncologist will advise on the most appropriate duration for your specific situation.
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