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The brakes and accelerators on immune cells, drawn where they sit: receptors on the T cell, NK cell and macrophage, their ligands on the tumour cell or antigen-presenting cell, and the enzymes and secreted signals in between. Pink means an approved drug exists against it.
Hover or focus a node for where it is expressed and its best drug; click for its row. Lines join partners.
approved drug against itInhibitory brakeCo-stimulatory acceleratorLigand on the other cellDon't eat me pairMetabolic brakeSoluble signal
Brakes carried by the immune cell itself. When the receptor meets its ligand on a tumour cell or an antigen-presenting cell, the T cell or NK cell stands down. Antibodies that block the receptor release the brake.
“PD-1 and CTLA-4 antibodies shaped treatment, most patients still show primary or adaptive resistance, and LAG-3, TIM-3, TIGIT and VISTA are the next checkpoints characterised.” Qin et al. 2019, Mol Cancer: novel immune checkpoint targets beyond PD-1 and CTLA-4
Antigen-activated T cells; delivers inhibitory signals on binding PD-L1 or PD-L2. UniProt Q15116
Activated T cells, at 30- to 50-fold lower surface levels than CD28; widely expressed with the highest levels in lymphoid tissues. UniProt P16410
Primarily activated T cells and a subset of NK cells. UniProt P18627
Th1 lymphocytes, regulatory T cells after TCR stimulation, dendritic cells and NK cells; also epithelial tissues. UniProt Q8TDQ0
Low levels on peripheral memory and regulatory CD4 T cells and NK cells, up-regulated on activation (protein level). UniProt Q495A1
Lymphocytes; an inhibitory receptor that dampens antigen-receptor signalling through SHP-1 and SHP-2. UniProt Q7Z6A9
Myeloid cells including CD11b monocytes and CD66b neutrophils, at low levels on CD4 and CD8 T cells and a subset of NK cells; not on B cells (protein level). UniProt Q9H7M9
Predominantly NK cells, with CD94; subsets of intraepithelial and memory CD8 T cells (protein level). UniProt P26715
NK cells; receptors for HLA-C alleles that inhibit NK-cell lysis. UniProt P43626
Activated T and NK cells; expressed on normal T-cell lines and clones and at very low levels on activated B cells. UniProt P40200
Low levels on freshly isolated T and NK cells, predominantly memory and effector CD8 T cells and both CD16-positive and CD16-negative NK cells; not on B cells, naive or helper T cells, monocytes or neutrophils (protein level). UniProt Q6DKI7
The other half of each pair. Tumours borrow these molecules from normal tissue so that the brakes on nearby T cells are pressed. Blocking the ligand works as well as blocking the receptor for PD-1.
Activated T and B cells, dendritic cells, keratinocytes and monocytes; widely expressed in tissue, highest in lung, liver and pituitary. UniProt Q9NZQ7
Highly expressed in heart, placenta, pancreas, lung and liver; weakly in spleen, lymph nodes and thymus. UniProt Q9BQ51
The surface of antigen-presenting cells. UniProt P33681
The surface of antigen-presenting cells. UniProt P42081
Professional antigen-presenting cells: macrophages, dendritic cells and B cells; thymic epithelial cells (protein level). UniProt P01903
Liver-specific under normal conditions; secreted by hepatocytes and certain tumour cells, and binds LAG-3 independently of MHC class II. UniProt Q08830
Peripheral blood leukocytes and lymphatic tissues; lung, liver, breast and kidney, with higher levels in tumour endothelial cells than normal endothelium (protein level). UniProt O00182
Columnar epithelial cells of the colon (protein level); granulocytes and lymphocytes, T cells carrying the long cytoplasmic isoforms. UniProt P13688
Barely or weakly expressed in normal human tissues but frequently over-expressed in malignant tumours; the ligand for the co-stimulatory receptor CD226 and the co-inhibitory receptors TIGIT and CD96 on NK and T cells. Kučan Brlić et al. 2017, Cell Mol Immunol: CD155, an onco-immunologic molecule
Ubiquitous; a co-stimulator through CD226 and a co-inhibitor through PVRIG, the two binding competitively. UniProt Q92692
Widely expressed, highest in lung, spleen and thymus; a subpopulation of B cells and monocytes, and naive T cells. UniProt Q92956
Endothelial cells of all vessel types outside lymphoid tissue; in lymphoid organs, endothelial venules, B and T cells, monocytes, macrophages, NK cells and megakaryocytes (protein level). UniProt P13747
Signals a cell shows to macrophages to say it is self and should not be eaten. Tumours over-express them; blocking the pair lets macrophages engulf the cancer cell.
“The CD24-Siglec-10 interaction inhibits macrophage-mediated phagocytosis as well as NK-cell cytotoxicity.” Panagiotou et al. 2022, Cancers: CD24 as a target for cancer immunotherapy
Very broadly distributed on normal adult tissues as well as ovarian tumours, especially abundant in some epithelia and the brain. UniProt Q08722
Myeloid cells but not T cells; ubiquitous at lower levels, highly expressed in brain. UniProt P78324
B cells and the T-cell surface; erythroleukaemia and small-cell lung carcinoma cell lines. UniProt P25063
Peripheral blood leukocytes: eosinophils, monocytes and an NK-cell subpopulation; an inhibitory receptor that recruits phosphatases on ligand binding. UniProt Q96LC7
B cells, monocytes and myeloid, plasmacytoid and tolerogenic dendritic cells; decidual macrophages and NK cells (protein level). UniProt Q8NHL6
Monocytes, at lower levels myeloid and plasmacytoid dendritic cells; tolerogenic IL-10-producing dendritic cells, myeloid-derived suppressor cells, B cells and low levels in NK cells. UniProt Q8N423
Accelerators rather than brakes. These receptors tell a T cell, or the dendritic cell that primes it, to go harder; the drugs are agonists that press them, or bispecifics that press them only where the other arm has found the tumour.
“CD40 activation licenses dendritic cells to promote antitumour T-cell activation and re-educates macrophages to destroy tumour stroma.” Vonderheide 2020, Annu Rev Med: CD40 agonist antibodies in cancer immunotherapy
T cells and plasma cells, not less mature B cells; the receptor for CD80 and CD86 that amplifies T-cell receptor signals. UniProt P10747
Activated and antigen-experienced T cells; highly expressed on tonsillar T cells in germinal centres. UniProt Q9Y6W8
Activated T cells; OX40 ligation augments CD4 and CD8 T-cell clonal expansion, effector differentiation and survival. Croft 2009, Immunol Rev: OX40-mediated co-stimulation
The surface of activated T cells; signalling enhances CD8 T-cell survival, cytotoxicity and mitochondrial activity. UniProt Q07011
Lymph node and peripheral blood leukocytes, weakly in spleen. UniProt Q9Y5U5
Most T lymphocytes, also NK and B cells; a co-stimulatory receptor activated by CD70 on B cells. UniProt P26842
B cells and primary carcinomas (UniProt); agonists license dendritic cells and re-educate macrophages. Vonderheide 2020, Annu Rev Med: CD40 agonist antibodies in cancer immunotherapy
Enzymes and receptors that change the chemistry around the tumour: they use up tryptophan or turn spilt ATP into adenosine, and either change starves or sedates T cells.
“CD39 and CD73 are cell-surface enzymes that catabolise extracellular ATP into adenosine; ectonucleotidases and adenosine receptors have emerged as therapeutic targets.” Allard et al. 2019, Immunol Rev: targeting the CD73-adenosine axis
Mature dendritic cells in lymphoid organs, some epithelial cells of the female genital tract, endothelial cells of term placenta and lung parenchyma; weak in most normal tissues but inducible. UniProt P14902
Catalyses the same tryptophan-to-kynurenine commitment step as IDO1; the cited review treats IDO1 and TDO2 together as drivers of tumour immune escape. UniProt gives no tissue distribution. Cheong and Sun 2018, Trends Pharmacol Sci: the IDO1/TDO2-kynurenine-AhR pathway
Broadly expressed; the ectonucleotidase that finishes the breakdown of extracellular ATP into adenosine. Allard et al. 2019, Immunol Rev: targeting the CD73-adenosine axis
Primarily activated lymphoid cells; also endothelium, and highly in placenta, lung, skeletal muscle and kidney. UniProt P49961
Broadly expressed adenosine receptor; G-protein coupled, raising cyclic AMP in the cells that carry it. Allard et al. 2019, Immunol Rev: targeting the CD73-adenosine axis
Relatives of PD-L1 and CD80 whose receptors are only partly known. Because tumours over-express them, most drugs treat them as an address for an antibody-drug conjugate rather than as a brake to release.
“B7-H3, B7x (B7-H4) and HHLA2 form the third phylogenetic group of the B7-CD28 family, with antagonistic antibodies and agonistic fusion proteins emerging for cancer.” Janakiram et al. 2017, Immunol Rev: the third group of the B7-CD28 family
Ubiquitous transcript but not detectable on peripheral blood lymphocytes or granulocytes; weak on resting monocytes, present on monocyte-derived dendritic cells and sinonasal epithelium. UniProt Q5ZPR3
Over-expressed in breast, ovarian, endometrial, renal cell and non-small-cell lung cancers; on activated T and B cells, monocytes and dendritic cells but not most normal tissues (protein level). UniProt Q7Z7D3
High in colon, kidney, testis, lung and pancreas; among immune cells, B cells, dendritic cells and macrophages, not T cells. UniProt Q9UM44
Not receptors but secreted signals that quieten immune cells across a whole tumour. The cited review frames them as immunosuppressive cytokines rather than checkpoints in the strict sense; they are listed here because the drugs against TGF-beta are fused to checkpoint antibodies.
“HPV up-regulates IL-10 and TGF-beta1 to produce a local immunosuppressive environment that inhibits the antitumour immune response.” Torres-Poveda et al. 2014, Infect Agent Cancer: IL-10 and TGF-beta1 in local immunosuppression
Stored latent in the extracellular matrix; highly expressed in bone and articular cartilage (UniProt). Up-regulated with IL-10 in HPV-driven cervical lesions to form a local immunosuppressive environment. Torres-Poveda et al. 2014, Infect Agent Cancer: IL-10 and TGF-beta1 in local immunosuppression
Produced by T cells, macrophages, mast cells and other cell types; a major anti-inflammatory cytokine signalling through IL10RA/IL10RB to STAT3. UniProt P22301
Sources. Identifiers from the HGNC REST API; expression from the UniProt tissue-specificity or function comment for the accession named on each row, or from the review cited; drug statuses from the drug records linked (each carries its own approvals and sources); phases for agents without a record here, and every stopped programme, from the ClinicalTrials.gov study cited, quoting the reason the registry gives. Where nothing was found the row says so. Taxonomy in src/data/checkpoint-map.ts.