# CTLA-4 and PD-1 Pathways: Similarities, Differences, and Implications of Their Inhibition

Source: https://onco.cc/key-papers/paper-pd-1-nsclc-am-j-clin-oncol-2016/  
OnCo record `paper-pd-1-nsclc-am-j-clin-oncol-2016` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Review on PD-1 in Non-small-cell lung cancer, in American journal of clinical oncology (2016), one of the most cited Europe PMC records with PD-1 in its title.

## Summary

The cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed death 1 (PD-1) immune checkpoints are negative regulators of T-cell immune function. Inhibition of these targets, resulting in increased activation of the immune system, has led to new immunotherapies for melanoma, non-small cell lung cancer, and other cancers. Ipilimumab, an inhibitor of CTLA-4, is approved for the treatment of advanced or unresectable melanoma. Nivolumab and pembrolizumab, both PD-1 inhibitors, are approved to treat patients with advanced or metastatic melanoma and patients with metastatic, refractory non-small cell lung cancer. In addition the combination of ipilimumab and nivolumab has been approved in patients with BRAF WT metastatic or unresectable melanoma. The roles of CTLA-4 and PD-1 in inhibiting immune responses, including antitumor responses, are largely distinct. CTLA-4 is thought to regulate T-cell proliferation early in an immune response, primarily in lymph nodes, whereas PD-1 suppresses T cells later in an immune response, primarily in peripheral tissues. The clinical profiles of immuno-oncology agents inhibiting these 2 checkpoints may vary based on their mechanistic differences. This article provides an overview of the CTLA-4 and PD-1 pathways and implications of their inhibition in cancer therapy.

Indexed on Europe PMC as PubMed record 26558876 (DOI 10.1097/coc.0000000000000239). Its title names PD-1 and its text names Non-small-cell lung cancer; PubMed types it as a review (review-article, Review). It was matched automatically to the idea "Give immunotherapy in the morning" and no figure has been checked by an editor.

## Fields

- Kind: Key paper
- Last checked: 2026-09-22
- Tags: europepmc-ingest
- Journal: American journal of clinical oncology
- Year: 2016
- DOI: 10.1097/coc.0000000000000239
- Authors: Buchbinder EI, Desai A
- What it means: One of the most cited reviews Europe PMC returns for PD-1 in Non-small-cell lung cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.
- Caveats: Matched by PD-1 in the title and Non-small-cell lung cancer in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.; A review summarises other studies; the primary reports it cites are the evidence.

## Sources

- Am J Clin Oncol 2016: https://doi.org/10.1097/coc.0000000000000239
- PubMed: https://pubmed.ncbi.nlm.nih.gov/26558876/
- Europe PMC: https://europepmc.org/article/MED/26558876

## Connected records

- journals: [American journal of clinical oncology](https://onco.cc/journals/american-journal-of-clinical-oncology/)
- ideas: [Give immunotherapy in the morning](https://onco.cc/ideas/idea-chronotherapy-immunotherapy/), [Microbiome transplant as a routine immunotherapy adjunct](https://onco.cc/ideas/idea-microbiome-io-fmt/)

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