Immune checkpoints

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

• Tifcemalimab (anti-BTLA) with toripalimab is in a phase 3 consolidation study in small-cell lung cancer (recruiting). ClinicalTrials.gov NCT06095583

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

• HMBD-002 (anti-VISTA) completed a phase 1 study alone and with pembrolizumab. ClinicalTrials.gov NCT05082610
• CI-8993 (anti-VISTA) completed a phase 1 study in advanced solid tumours. ClinicalTrials.gov NCT04475523

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

• Lirilumab (anti-KIR2DL1/2/3) reached phase 1/2 with nivolumab in solid tumours. ClinicalTrials.gov NCT01714739

Activated T and NK cells; expressed on normal T-cell lines and clones and at very low levels on activated B cells. UniProt P40200

• GSK6097608 (anti-CD96) is in phase 2 platform studies with dostarlimab in non-small-cell lung cancer. ClinicalTrials.gov NCT05565378

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

• COM701 (anti-PVRIG) completed phase 1/2 with a TIGIT antibody and nivolumab and is recruiting in platinum-sensitive ovarian cancer. ClinicalTrials.gov NCT06888921

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

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

• IMM47 (anti-CD24) entered a phase 1 study in advanced solid tumours; the registry status is unknown. ClinicalTrials.gov NCT05985083

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

• NGM707 (anti-LILRB1/LILRB2) reached phase 1/2 with pembrolizumab; a later phase 2 study was withdrawn by the sponsor. ClinicalTrials.gov NCT04913337

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

• MK-4830 (anti-LILRB2) is in phase 2 with pembrolizumab, including a completed study with chemotherapy in ovarian cancer. ClinicalTrials.gov NCT05446870

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

• BMS-986156 (GITR agonist) completed phase 1/2 alone and with nivolumab. ClinicalTrials.gov NCT02598960

Most T lymphocytes, also NK and B cells; a co-stimulatory receptor activated by CD70 on B cells. UniProt P26842

• Varlilumab (CD27 agonist) reached phase 2 with nivolumab in aggressive B-cell lymphoma. ClinicalTrials.gov NCT03038672

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

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

• No TDO2-selective agent was found in ClinicalTrials.gov under the drug names the corpus knows; the LY3381916 study is an IDO1 programme and was terminated for business reasons. ClinicalTrials.gov NCT03343613

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

• TTX-030 (anti-CD39) completed a phase 2 study with chemotherapy, with or without budigalimab, in first-line metastatic pancreatic cancer. ClinicalTrials.gov NCT06119217

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

• Ciforadenant (A2A antagonist) is in phase 1b/2 with ipilimumab and nivolumab. ClinicalTrials.gov NCT05501054
• Etrumadenant (A2A/A2B antagonist) is in phase 2 combinations in pancreatic cancer. ClinicalTrials.gov NCT06048484
• Inupadenant (A2A antagonist) is in phase 2 with chemotherapy in non-squamous non-small-cell lung cancer. ClinicalTrials.gov NCT05403385

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

• No HHLA2-directed agent is in the corpus, and none was looked up in the registry for this map; the family review lists antagonistic antibodies and agonistic fusion proteins as emerging. Janakiram et al. 2017, Immunol Rev: the third group of the B7-CD28 family

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