biology

PD-1 and PD-L1 inhibitors

PD-1 and PD-L1 inhibitors is a biology topic covered in the lgStudy science library. This page brings together a partial reference excerpt, illustrations, worked examples, real-world applications and a short study plan, so you can understand PD-1 and PD-L1 inhibitors rather than just read about it. In short: PD-1 inhibitors and PD-L1 inhibitors are a group of checkpoint inhibitor anticancer drugs that block the activity of PD-1 and PD-L1 immune checkpoint proteins present on the surface of cells. Immune checkpoint inhibitors are emerging as a front-line treatment for several types of cancer.

Key takeaways

PD-1 and PD-L1 inhibitors belongs to biology; place it in that map before memorising details.
Learn the definition first, then one example that makes the definition concrete.
Connect PD-1 and PD-L1 inhibitors to a quantity you can measure, compute or draw — that is where exam questions come from.
Reproduce the core statement of PD-1 and PD-L1 inhibitors from memory before moving on to harder problems.

Reference excerpt

PD-1 inhibitors and PD-L1 inhibitors are a group of checkpoint inhibitor anticancer drugs that block the activity of PD-1 and PD-L1 immune checkpoint proteins present on the surface of cells. Immune checkpoint inhibitors are emerging as a front-line treatment for several types of cancer. PD-1 and PD-L1 inhibitors act to inhibit the association of the programmed death-ligand 1 (PD-L1) with its receptor, programmed cell death protein 1 (PD-1). The interaction of these cell surface proteins is involved in the suppression of the immune system and occurs following infection to limit the killing of bystander host cells and prevent autoimmune disease. This immune checkpoint is also active in pregnancy, following tissue allografts, and in different types of cancer.

History The concept of blocking PD-1 and PD-L1 for the treatment of cancer was first published in 2001. Pharmaceutical companies began attempting to develop drugs to block these molecules, and the first clinical trial was launched in 2006, evaluating nivolumab. As of 2017, more than 500 clinical trials involving PD-1 and PD-L1 inhibitors have been conducted in more than 20,000 patients. By the end of 2017, PD-1/PD-L1 inhibitors had been approved for the treatment of nine forms of cancer.

Cancer immunotherapy In the cancer disease state, the interaction of PD-L1 on the tumor cells with PD-1 on a T-cell reduces T-cell function signals to prevent the immune system from attacking the tumor cells. Use of an inhibitor that blocks the interaction of PD-L1 with the PD-1 receptor can prevent the cancer from evading the immune system in this way. Several PD-1 and PD-L1 inhibitors are being trialled within the clinic for use in advanced melanoma, non-small cell lung cancer, renal cell carcinoma, bladder cancer and Hodgkin lymphoma, amongst other cancer types. Immunotherapy with these immune checkpoint inhibitors appears to shrink tumours in a higher number of patients across a wider range of tumour types and is associated with lower toxicity levels than other immunotherapies, with durable responses. However, de-novo and acquired resistance is still seen in a large proportion of patients. Hence PD-L1 inhibitors are considered to be the most promising drug category for many different cancers. Not all patients respond to PD-1/PD-L1 inhibitors. The FDA has approved several assays to measure the level of PD-L1 expressed by tumor cells, in order to predict the likelihood of response to an inhibitor. PD-L1 levels have been found to be highly predictive of response. Higher tumor mutational burden is also predictive of response to anti-PD-1/PD-L1 agents. However, these markers are far from perfect, and there is a clinical interest in the search for new biomarkers predictive of the benefit of these therapies beyond PD-L1 and TMB levels. Emerging evidence suggests that the gut microbiome may also provide predictive information for response to immune checkpoint blockade. In a multi-regional study 674 patients with resected high-risk melanoma receiving adjuvant immune checkpoint blockade, pre-treatment gut bacterial markers were associated with recurrence, with prediction performing best when patients were compared within groups matched for overall gut microbiome composition, suggesting that microbiome-based biomarkers may be informative but context dependent. PD-1 and PD-L1 inhibitors are closely related to CTLA4 (cytotoxic T-lymphocyte-associated protein 4) inhibitors, such as ipilimumab. PD-1 and CTLA-4 are both expressed on activated T cells, but at different phases of immune response. Current clinical trials are evaluating anti-PD-1 and PD-L1 drugs in combination with other immunotherapy drugs blocking LAG3, B7-H3, KIR, OX40, PARP, CD27, and ICOS.

Therapeutics

PD-1 Pembrolizumab (Keytruda, formerly MK-3475 and lambrolizumab) was developed by Merck and first approved by the Food and Drug Administration in 2014 for the treatment of melanoma. It was later approved for metastatic non-small cell lung cancer and head and neck squamous cell carcinoma. In 2017, it became the first immunotherapy drug approved for use based on the genetic mutations of the tumor rather than the site of the tumor. It was shown that patients with higher non-synonymous mutation burden in their tumors respond better to the treatment. Both their objective response rate and progression-free survival was shown to be higher than in patients with low non-synonymous mutation burden. Nivolumab (Opdivo) was developed by Bristol-Myers Squibb and first approved by the FDA in 2014 for the treatment of melanoma. It was later approved for squamous cell lung cancer, renal cell carcinoma, and Hodgkin's lymphoma. Cemiplimab (Libtayo) was developed by Regeneron Pharmaceuticals and first approved by the FDA in 2018 for the treatment of cutaneous squamous cell carcinoma (CSCC) or locally advanced CSCC who are not candidates for curative surgery or curative radiation. Dostarlimab (Jemperli) – was developed by GlaxoSmithKline and was first approved for the treatment of mismatch repair deficient (dMMR) recurrent or advanced endometrial cancer by the FDA in April of 2021. On August 17, 2021, the FDA granted accelerated approval for the treatment of mismatch repair deficient (dMMR) recurrent or advanced solid tumors. Retifanlimab (Zynyz) was developed by Incyte and first granted accelerated approval by the FDA in March 2023 for the treatment of Merkel cell carcinoma (MCC). Toripalimab (Loqtorzi) is a humanized IgG4 monoclonal antibody against PD-1 approved in China in 2018 and in the United States in 2023. Tislelizumab (Tevimbra) is a humanized IgG4 anti–PD-1 monoclonal antibody approved in China in 2019 and in the United States in 2024 for certain gastrointestinal cancers. Serplulimab (Hetronifly, HANSIZHUANG, HLX10) is a novel anti-PD-1 monoclonal antibody approved for medical use in China in 2022. It has been approved by the National Medical Products Administration (NMPA) for the treatment of squamous non-small cell lung cancer (sqNSCLC), extensive-stage small cell lung cancer (ES-SCLC), esophageal squamous cell carcinoma (ESCC), non-squamous non-small cell lung cancer (nsqNSCLC) and gastric cancer (GC), making it the world’s first anti-PD-1 mAb for the first-line treatment of SCLC and for the treatment of perioperative gastric cancer .

Experimental Currently, many PD-1 inhibitors are under development:

… excerpt ends here. Continue reading the full article.

Illustrations

Worked examples

Example 1 — a first encounter with PD-1 and PD-L1 inhibitors

Start with the simplest possible case. Write down what PD-1 and PD-L1 inhibitors claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In biology, the smallest case is usually a single object, a single equation or a single measurement. Check that every symbol or term in your sentence has a meaning in that case.

Example 2 — changing one variable

Take the situation from Example 1 and change exactly one quantity: double it, halve it, or set it to zero. Predict what should happen to PD-1 and PD-L1 inhibitors before you calculate. Comparing your prediction with the result is the fastest way to find out whether you understand the idea or only the words.

Example 3 — an exam-style question

Typical questions about PD-1 and PD-L1 inhibitors ask you to (a) state it precisely, (b) apply it to given data, and (c) explain a limitation. Practise writing all three answers in under five minutes; the third part is what separates a full-mark answer from an average one.

Applications of PD-1 and PD-L1 inhibitors

In research: PD-1 and PD-L1 inhibitors appears in biology research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry: Engineering practice reuses PD-1 and PD-L1 inhibitors in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom: PD-1 and PD-L1 inhibitors is common in secondary-school and first-year university syllabi. It links to neighbouring topics Cancer immunotherapy, Human proteins, so understanding it makes those chapters shorter.
In everyday life: Look for PD-1 and PD-L1 inhibitors outside the textbook — in sport, cooking, traffic, electronics or the sky above you. An example you found yourself is remembered far longer than one you were given.

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How to study PD-1 and PD-L1 inhibitors in 20 minutes

Read the reference excerpt below once, without taking notes.
Close the page and write down what PD-1 and PD-L1 inhibitors means in your own words.
Compare your version with the excerpt and mark what you missed.
Work through the three examples above with pen and paper.
Explain PD-1 and PD-L1 inhibitors out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is PD-1 and PD-L1 inhibitors in simple terms?

Why does PD-1 and PD-L1 inhibitors matter?

Because it connects several biology ideas at once: it gives you a definition you can apply, a quantity you can calculate, and a way to check whether a result is plausible.

How should I study PD-1 and PD-L1 inhibitors?

Read the excerpt, restate it from memory, then work through the examples and applications listed on this page. The five-step study plan above takes about twenty minutes.

What does this page cover?

It gives you a compact reference excerpt plus original lgStudy explanations, examples, applications and study material on PD-1 and PD-L1 inhibitors.