# CTLA-4

Source: https://onco.cc/targets/ctla4/  
OnCo record `ctla4` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

The first immune brake ever targeted for cancer; releasing it won a Nobel Prize and cures a fraction of melanomas.

## Summary

CTLA-4 is a checkpoint on activated and regulatory T cells that competes with CD28 for B7 ligands during T-cell priming; antibodies against it broaden the T-cell response and, through Fc effector function, deplete regulatory T cells inside tumours. Ipilimumab (2011) was the first checkpoint inhibitor, and the concept later shared a Nobel Prize. Combined with nivolumab it yields 10-year survival near 50 percent in advanced melanoma (CheckMate 067), and the pair is used in RCC, MSI-high colorectal cancer, HCC and mesothelioma. The cost is frequent immune-related toxicity such as colitis and hypophysitis, and because it acts on immune cells there is no tumour biomarker to select patients. Fc-engineered and probody CTLA-4 antibodies aim to reduce toxicity. Releasing this brake was the first proof that the immune system can cure some cancers.

## Fields

- Kind: Target
- Last checked: 2026-09-04
- Tags: checkpoint
- Symbol: CTLA4
- Class: checkpoint
- Biology: Competes with CD28 for B7 ligands during T-cell priming; also depletes regulatory T cells via Fc effector function.
- Where found: Activated and regulatory T cells

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/CTLA-4
- Wikipedia: https://en.wikipedia.org/wiki/CTLA-4

## Connected records

- cancers: [Advanced melanoma (unresectable stage III and stage IV)](https://onco.cc/cancers/advanced-melanoma/), [Cervical cancer](https://onco.cc/cancers/cervical/), [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Hepatocellular carcinoma](https://onco.cc/cancers/hcc/), [Melanoma](https://onco.cc/cancers/melanoma/), [Merkel cell carcinoma](https://onco.cc/cancers/merkel-cell-carcinoma/), [Mesothelioma](https://onco.cc/cancers/mesothelioma/), [Mismatch repair deficient (MSI-high) pancreatic ductal adenocarcinoma](https://onco.cc/cancers/msi-high-pdac/), [Mismatch-repair deficient (MSI-high) colorectal cancer](https://onco.cc/cancers/msi-high-colorectal/), [Mucosal melanoma](https://onco.cc/cancers/mucosal-melanoma/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/), [Oesophageal cancer](https://onco.cc/cancers/esophageal/), [PD-L1-high non-small-cell lung cancer without a driver mutation](https://onco.cc/cancers/pdl1-high-nsclc/), [Renal cell carcinoma](https://onco.cc/cancers/rcc/), [Stage III melanoma (after surgery)](https://onco.cc/cancers/stage-iii-melanoma/), [Uveal melanoma](https://onco.cc/cancers/uveal-melanoma/), [Vascular tumours (angiosarcoma, epithelioid haemangioendothelioma, kaposiform haemangioendothelioma)](https://onco.cc/cancers/vascular-tumours/)
- drugs: [ADG126](https://onco.cc/drugs/adg126/), [BA3071](https://onco.cc/drugs/ba3071/), [BCD-217](https://onco.cc/drugs/bcd-217/), [Botensilimab](https://onco.cc/drugs/botensilimab/), [Cadonilimab](https://onco.cc/drugs/cadonilimab/), [Gotistobart](https://onco.cc/drugs/gotistobart/), [Ipilimumab](https://onco.cc/drugs/ipilimumab/), [JK08](https://onco.cc/drugs/jk08/), [Lorigerlimab](https://onco.cc/drugs/lorigerlimab/), [Tremelimumab](https://onco.cc/drugs/tremelimumab/)
- companies: [Agenus](https://onco.cc/companies/agenus/), [Xilio Therapeutics](https://onco.cc/companies/xilio-therapeutics/)
- pathways: [Hepatocellular carcinoma (KEGG map)](https://onco.cc/pathways/hepatocellular-carcinoma-signalling/), [Mismatch repair & microsatellite instability](https://onco.cc/pathways/mismatch-repair-msi/), [PD-1 / PD-L1 immune checkpoint & T-cell activation](https://onco.cc/pathways/pd1-checkpoint/), [T-cell exhaustion](https://onco.cc/pathways/t-cell-exhaustion/), [The cancer-immunity cycle](https://onco.cc/pathways/cancer-immunity-cycle/), [Tumour microenvironment (TME)](https://onco.cc/pathways/tumor-microenvironment/)
- trials: [CA184-043](https://onco.cc/trials/ca184-043-ipilimumab/), [CheckMate 142](https://onco.cc/trials/checkmate-142/), [CheckMate 204](https://onco.cc/trials/checkmate-204/), [CheckMate 238](https://onco.cc/trials/checkmate-238/), [CheckMate 648](https://onco.cc/trials/checkmate-648/), [CheckMate 8HW](https://onco.cc/trials/checkmate-8hw/), [CheckMate 9DW](https://onco.cc/trials/checkmate-9dw/), [CheckMate 9LA](https://onco.cc/trials/checkmate-9la/), [COMPASSION-16 / AK104-303](https://onco.cc/trials/compassion-16/), [DREAMseq (ECOG-ACRIN EA6134)](https://onco.cc/trials/dreamseq/), [HIMALAYA](https://onco.cc/trials/himalaya/), [KEYNOTE-006](https://onco.cc/trials/keynote-006/), [NADINA](https://onco.cc/trials/nadina/)
- ideas: [Making microsatellite-stable colorectal cancer immunotherapy-responsive](https://onco.cc/ideas/idea-immunotherapy-mss-crc/), [Select microsatellite stable patients for immunotherapy by a measured immune biomarker, not by how many treatments they have already failed](https://onco.cc/ideas/idea-crc-mss-immunotherapy-by-biomarker-not-by-line/)
- key papers: [ASCO 2021 guideline: how to recognise and manage the immune-related side effects of checkpoint inhibitors](https://onco.cc/key-papers/paper-asco-irae-guideline-jco-2021/), [Autophagy promotes immune evasion of pancreatic cancer by degrading MHC-I](https://onco.cc/key-papers/paper-yamamoto-nature/), [Botensilimab plus balstilimab in relapsed/refractory microsatellite stable metastatic colorectal cancer: a phase 1 trial](https://onco.cc/key-papers/paper-bullock-botensilimab-balstilimab-mss-colorectal-nat-med-2024/), [CheckMate 067 at ten years: nivolumab plus ipilimumab produces long-term survival in half of patients with advanced melanoma](https://onco.cc/key-papers/paper-checkmate-067-10-year-nejm-2025/), [Durvalumab with or without tremelimumab for patients with metastatic pancreatic ductal adenocarcinoma: a phase 2 randomized clinical trial](https://onco.cc/key-papers/paper-oreilly-durvalumab-tremelimumab-pancreatic-jama-oncol-2019/), [Hodi 2010: ipilimumab, the first checkpoint inhibitor, extends survival in metastatic melanoma](https://onco.cc/key-papers/paper-hodi-ipilimumab-melanoma-nejm-2010/), [KEYNOTE-006 (Robert 2015): pembrolizumab versus ipilimumab in advanced melanoma](https://onco.cc/key-papers/paper-keynote-006-pembrolizumab-ipilimumab-melanoma-nejm-2015/), [Leach, Krummel and Allison: releasing the CTLA-4 brake makes mice reject tumours](https://onco.cc/key-papers/paper-leach-allison-ctla4-blockade-science-1996/), [NADINA: two doses of ipilimumab plus nivolumab before surgery beat a year of nivolumab after surgery in stage III melanoma](https://onco.cc/key-papers/paper-nadina-nejm-2024/), [NICHE-2: a month of nivolumab and ipilimumab before surgery clears mismatch-repair-deficient colon cancer in most patients](https://onco.cc/key-papers/paper-niche-2-nejm-2024/), [Nivolumab plus Ipilimumab in Lung Cancer with a High Tumor Mutational Burden](https://onco.cc/key-papers/paper-checkmate-227-n-engl-j-med-2018/), [Nivolumab plus ipilimumab in microsatellite-instability-high metastatic colorectal cancer (CheckMate 8HW)](https://onco.cc/key-papers/paper-andre-checkmate-8hw-nivolumab-ipilimumab-nejm-2024/), [Pardoll 2012: the blockade of immune checkpoints in cancer immunotherapy](https://onco.cc/key-papers/paper-pardoll-immune-checkpoint-blockade-nrc-2012/), [Phase 2 trial of single agent ipilimumab (anti-CTLA-4) for locally advanced or metastatic pancreatic adenocarcinoma](https://onco.cc/key-papers/paper-royal-ipilimumab-pancreatic-j-immunother-2010/), [Ribas and Wolchok 2018: cancer immunotherapy using checkpoint blockade](https://onco.cc/key-papers/paper-ribas-wolchok-checkpoint-blockade-science-2018/), [Rohaas 2022: the first randomised trial of TIL therapy, against ipilimumab, in advanced melanoma](https://onco.cc/key-papers/paper-rohaas-til-vs-ipilimumab-nejm-2022/), [Targeting CXCL12 from FAP-expressing carcinoma-associated fibroblasts synergizes with anti-PD-L1 immunotherapy in pancreatic cancer](https://onco.cc/key-papers/paper-feig-cxcl12-fap-cafs-t-cell-exclusion-pnas-2013/)
- roadmaps: [Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation](https://onco.cc/roadmaps/colorectal-roadmap/)
- technologies: [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/)
- people: [F. Stephen Hodi](https://onco.cc/people/f-stephen-hodi/), [Georgina V. Long](https://onco.cc/people/georgina-long/), [Ghassan K. Abou-Alfa](https://onco.cc/people/ghassan-abou-alfa/), [Heinz-Josef Lenz](https://onco.cc/people/heinz-josef-lenz/), [James P. Allison](https://onco.cc/people/james-allison/), [Jedd D. Wolchok](https://onco.cc/people/jedd-wolchok/), [Jeffrey A. Bluestone](https://onco.cc/people/jeffrey-bluestone/), [Michael A. Postow](https://onco.cc/people/michael-postow/), [Padmanee Sharma](https://onco.cc/people/padmanee-sharma/), [Paul Baas](https://onco.cc/people/paul-baas/), [Robert J. Motzer](https://onco.cc/people/robert-motzer/), [Sharon Belvin](https://onco.cc/people/sharon-belvin/), [Tak W. Mak](https://onco.cc/people/tak-mak/), [Thierry André](https://onco.cc/people/thierry-andre/)
- bottlenecks: [Cold tumours and the immunosuppressive microenvironment](https://onco.cc/bottlenecks/b-tme-immunosuppression/)
- terms: [Checkpoint (two meanings)](https://onco.cc/terms/checkpoint/), [Hallmark: avoiding immune destruction](https://onco.cc/terms/avoiding-immune-destruction/), [Immune checkpoint](https://onco.cc/terms/immune-checkpoint/), [Immune surveillance and cancer immunoediting](https://onco.cc/terms/immune-surveillance-immunoediting/), [T cell](https://onco.cc/terms/t-cell/)
- targets: [CD28](https://onco.cc/targets/cd28/), [CD80 (B7-1)](https://onco.cc/targets/cd80/), [CD86 (B7-2)](https://onco.cc/targets/cd86/), [VISTA](https://onco.cc/targets/vista/)
- institutions: [Dartmouth Cancer Center](https://onco.cc/institutions/dartmouth-cancer-center/), [Istituto Nazionale Tumori IRCCS Fondazione G. Pascale](https://onco.cc/institutions/pascale-naples/)

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JSON: https://onco.cc/api/v1/entities/ctla4.json