Immunology · Transplant, tumors and immunotherapy

Tumor immunology and checkpoint inhibitors !

Process

The immune system can find and kill cancer cells; tumors learn to hide or switch immune cells off, and new drugs release the brakes.

Updated 2026-11-01

Key points

CTLA-4 acts early, in the lymph node, competing with CD28 for B7 (CD80/CD86); blocked by ipilimumab.
PD-1 on T cells binds PD-L1 on tumor cells and switches T cells off in the tissue; blocked by nivolumab and pembrolizumab (anti-PD-1) and atezolizumab and durvalumab (anti-PD-L1). Relatlimab blocks LAG-3.
Immune-related adverse events: colitis, hepatitis, pneumonitis, dermatitis, thyroiditis, hypophysitis, type 1 diabetes, myocarditis, nephritis; usually treated with corticosteroids.
NK cells kill cells that have lost MHC class I, a common tumor escape route from CD8 T cells.
CAR-T cells (for example anti-CD19 or anti-BCMA) can cause cytokine release syndrome (IL-6; treated with tocilizumab) and neurotoxicity.
Oncogenic viruses: HPV (cervix, oropharynx), EBV (Burkitt, nasopharyngeal), HHV-8 (Kaposi), HBV and HCV (liver), HTLV-1 (adult T-cell leukemia).

What it is

T cells and NK cells recognize tumor cells by abnormal proteins (neoantigens) or by missing MHC class I. Tumors that grow have escaped: they lose antigens or MHC, recruit regulatory cells and express brake molecules such as PD-L1. Immune checkpoint inhibitors block these brakes (CTLA-4, PD-1, PD-L1, LAG-3) and can produce lasting responses, at the price of autoimmune-like side effects.

Key facts

Tumor-specific antigens come from mutations or viral proteins; tumor-associated antigens (such as CEA or AFP) are normal proteins made in excess or at the wrong time, and serve as tumor markers.
Tumors with many mutations or mismatch repair defects tend to respond better to checkpoint inhibitors.
Intravesical BCG for early bladder cancer is a historic example of nonspecific immune stimulation against a tumor.
Immunosuppressed transplant recipients have more skin cancers and virus-driven cancers, showing that immune surveillance matters.

Step by step

Dying tumor cells release antigens that dendritic cells capture.
Dendritic cells carry them to the lymph node and prime T cells (signal 1 plus CD28–B7 costimulation).
Activated cytotoxic T cells travel through the blood and enter the tumor.
CD8 T cells recognize tumor peptides on MHC class I and kill the cell; NK cells kill cells missing MHC class I.
Tumors escape by losing MHC or antigens, expressing PD-L1, and recruiting regulatory T cells and suppressive myeloid cells (TGF-β, IL-10).
Checkpoint inhibitors block CTLA-4 or PD-1/PD-L1 so the T-cell attack can resume.

Checkpoint inhibitors

Target	Drugs	Where it acts	Examples of use
CTLA-4	Ipilimumab	Priming in lymph nodes	Melanoma, often combined with nivolumab
PD-1	Nivolumab, pembrolizumab	Effector T cells in the tumor	Melanoma, lung, kidney, head and neck cancers, Hodgkin lymphoma, tumors with mismatch repair deficiency
PD-L1	Atezolizumab, durvalumab, avelumab	Tumor and immune cells in the tumor	Lung, bladder and other cancers
LAG-3	Relatlimab (with nivolumab)	Exhausted T cells	Advanced melanoma

Test yourself

Think of the answer, then tap the question to see it.

How does ipilimumab differ from pembrolizumab in its target?

Ipilimumab blocks CTLA-4, acting mainly at T-cell priming in lymph nodes; pembrolizumab blocks PD-1, acting on effector T cells in the tumor.

Why can checkpoint inhibitors cause colitis, thyroiditis or hypophysitis?

Releasing T-cell brakes also lowers tolerance to self, so T cells attack normal organs (immune-related adverse events).

Which cell kills tumor cells that have lost MHC class I?

The natural killer (NK) cell, which is inhibited by MHC class I and attacks when it is missing.

Which cytokine drives cytokine release syndrome after CAR-T therapy, and which antibody blocks its receptor?

IL-6; tocilizumab blocks the IL-6 receptor.

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Microorganisms

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Educational content on the immune system; not a treatment or individual vaccination guide and no substitute for a health professional's advice. No doses are given.

Sources: Immune Checkpoint Inhibitors (National Cancer Institute (NCI), 2026); Immunotherapy to Treat Cancer (National Cancer Institute (NCI), 2026); Monoclonal Antibodies (National Cancer Institute (NCI), 2026).

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Representative model, for educational purposes only.