[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Immunology](https://durgical.com/en/immunology/) › [Transplant, tumors and immunotherapy](https://durgical.com/en/immunology/#a-transplant) › Tumor immunology and checkpoint inhibitors

[Immunology](https://durgical.com/en/immunology/) · [Transplant, tumors and immunotherapy](https://durgical.com/en/immunology/#a-transplant)

# 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 |

## Memory aid

CTLA-4 is the brake at the starting line (lymph node); PD-1 is the brake on the track (tumor). Checkpoint drugs lift the foot off the brake.

## 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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## Related

- [CD8⁺ cytotoxic T cell](https://durgical.com/en/immunology/cd8-cytotoxic-t-cell/)
- [Natural killer cell](https://durgical.com/en/immunology/natural-killer-cell/)
- [T-cell activation: two signals and superantigens](https://durgical.com/en/immunology/t-cell-activation-two-signals-and-superantigens/)
- [Regulatory T cell (Treg, FOXP3)](https://durgical.com/en/immunology/regulatory-t-cell/)
- [Monoclonal antibodies and biologics: naming and targets](https://durgical.com/en/immunology/monoclonal-antibodies-and-biologics-naming-and-targets/)
- [Immunosuppressants by mechanism (classes)](https://durgical.com/en/immunology/immunosuppressants-by-mechanism/)

## Microorganisms

- [Human papillomavirus](https://durgical.com/en/microbiology/human-papillomavirus/)
- [Epstein–Barr virus](https://durgical.com/en/microbiology/epstein-barr-virus/)
- [Human herpesvirus 8](https://durgical.com/en/microbiology/human-herpesvirus-8/)
- [Hepatitis B virus](https://durgical.com/en/microbiology/hepatitis-b-virus/)
- [Hepatitis C virus](https://durgical.com/en/microbiology/hepatitis-c-virus/)
- [Human T-lymphotropic virus type 1](https://durgical.com/en/microbiology/human-t-lymphotropic-virus-type-1/)

[← All of immunology](https://durgical.com/en/immunology/)

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](https://www.cancer.gov/about-cancer/treatment/types/immunotherapy/checkpoint-inhibitors) (National Cancer Institute (NCI), 2026); [Immunotherapy to Treat Cancer](https://www.cancer.gov/about-cancer/treatment/types/immunotherapy) (National Cancer Institute (NCI), 2026); [Monoclonal Antibodies](https://www.cancer.gov/about-cancer/treatment/types/immunotherapy/monoclonal-antibodies) (National Cancer Institute (NCI), 2026).

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License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/immunology/tumor-immunology-and-checkpoint-inhibitors/