Cancer immunotherapy by PD-1 blockade (Homo sapiens)

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T cellTumor cell1-34-6NucleusT-cell inducedPDL1 upregulationT cell activationGrowthProliferationSurvivalZAP70STAT3MHC IPTPN11IFNGNivolumabBATFCD274TislelizumabNFATC1PembrolizumabTRATumor-associatedantigenDurvalumabCD8ARas signalingPidilizumabLCKAMP-224AtezolizumabAvelumabMDX-1105PDCD1CD3DPDCD1LG2JUNPTRBPPPMHC IIBATFCD3ECD3GNFKB1PI3K signalingCD8BNFATC2NFATC3NFATC4NFAT5


Immune checkpoints are hardwired into the immune system and are crucial for maintaining self-tolerance. Tumors can use these checkpoints to protect themselves from immune system attacks.

One such immune checkpoint is PD-1 (programmed cell death 1 protein), which binds to its ligand PD-L1 and inhibits immune cell activity, including T cell activity. By upregulating PD-L1, cancer cells can inhibit T cells that might otherwise attack. One strategy for cancer immunotherapy is to block this kind of negative feedback, thereby increasing anti-cancer T-cell activity. For the PD-1 checkpoint, cancer immunotherapeutics block either the PD-1 receptor, or the PD-L1 ligand. The 2018 Nobel prize in Physiology or Medicine was awarded to jointly to James Allison and Tasuku Honjo for their discovery of cancer therapy by inhibition of negative immune regulation.

Based on and figure 4B in the review by Pardoll and figure 1 in the review by Sharpe and Pauken.

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  1. Sadreddini S, Baradaran B, Aghebati-Maleki A, Shanehbandi D, Fotouhi A, Aghebati-Maleki L; ''Immune checkpoint blockade opens a new way to cancer immunotherapy.''; J Cell Physiol, 2019 PubMed Europe PMC
  2. Pardoll DM; ''The blockade of immune checkpoints in cancer immunotherapy.''; Nat Rev Cancer, 2012 PubMed Europe PMC
  3. Sharpe AH, Pauken KE; ''The diverse functions of the PD1 inhibitory pathway.''; Nat Rev Immunol, 2018 PubMed Europe PMC
  4. Syed YY; ''Durvalumab: First Global Approval.''; Drugs, 2017 PubMed Europe PMC
  5. Schmid P, Adams S, Rugo HS, Schneeweiss A, Barrios CH, Iwata H, Diéras V, Hegg R, Im SA, Shaw Wright G, Henschel V, Molinero L, Chui SY, Funke R, Husain A, Winer EP, Loi S, Emens LA; ''Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer.''; N Engl J Med, 2018 PubMed Europe PMC
  6. Kaufman HL, Russell JS, Hamid O, Bhatia S, Terheyden P, D'Angelo SP, Shih KC, Lebbé C, Milella M, Brownell I, Lewis KD, Lorch JH, von Heydebreck A, Hennessy M, Nghiem P; ''Updated efficacy of avelumab in patients with previously treated metastatic Merkel cell carcinoma after ≥1 year of follow-up: JAVELIN Merkel 200, a phase 2 clinical trial.''; J Immunother Cancer, 2018 PubMed Europe PMC


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108119view10:24, 29 November 2019FehrhartOntology Term : 'cancer pathway' added !
105196view23:55, 18 July 2019Khanspersupdated placement of states
104541view23:36, 30 May 2019Khanspersadded missing xrefs
104342view22:34, 17 May 2019KhanspersModified title
104338view21:40, 17 May 2019KhanspersModified title
104336view21:25, 17 May 2019Khanspersadded xref
104335view21:18, 17 May 2019KhanspersModified description
104321view23:21, 16 May 2019Khanspersadded phosphosites
104320view23:04, 16 May 2019Khanspersremoved non-relevant and updated details
104317view21:32, 16 May 2019Khanspersdetails added
104152view00:23, 7 May 2019Khanspersadded lit ref
104151view00:21, 7 May 2019KhanspersModified description
104150view00:19, 7 May 2019KhanspersModified description
104108view19:23, 3 May 2019KhanspersModified description
104102view18:53, 3 May 2019KhanspersOntology Term : 'PW:0000023' removed !
104101view18:52, 3 May 2019KhanspersOntology Term : 'adaptive immune response pathway' added !
104100view18:52, 3 May 2019KhanspersOntology Term : 'immune response pathway' added !
104099view18:51, 3 May 2019KhanspersOntology Term : 'cancer' added !
104098view18:51, 3 May 2019KhanspersOntology Term : 'T cell' added !
104097view18:48, 3 May 2019KhanspersNew pathway

External references


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NameTypeDatabase referenceComment
AtezolizumabMetaboliteQ20707748 (Wikidata)
AvelumabMetaboliteQ21083261 (Wikidata)
BATFGeneProductENSG00000156127 (Ensembl)
CD274GeneProductENSG00000120217 (Ensembl)
CD3DGeneProductENSG00000167286 (Ensembl)
CD3EGeneProductENSG00000198851 (Ensembl)
CD3GGeneProductENSG00000160654 (Ensembl)
CD8AGeneProductENSG00000153563 (Ensembl)
CD8BGeneProductENSG00000172116 (Ensembl)
DurvalumabMetaboliteQ19904005 (Wikidata)
IFNGGeneProductENSG00000111537 (Ensembl)
JUNGeneProductENSG00000177606 (Ensembl)
LCKGeneProductENSG00000182866 (Ensembl)
MHC IProteinENSG00000206503 (Ensembl)
MHC IIProteinENSG00000196126 (Ensembl)
NFAT5GeneProductENSG00000102908 (Ensembl)
NFATC1GeneProductENSG00000131196 (Ensembl)
NFATC2GeneProductENSG00000101096 (Ensembl)
NFATC3GeneProductENSG00000072736 (Ensembl)
NFATC4GeneProductENSG00000100968 (Ensembl)
NFKB1GeneProductENSG00000109320 (Ensembl)
NivolumabMetaboliteQ7041828 (Wikidata)
PDCD1GeneProductENSG00000188389 (Ensembl)
PDCD1LG2GeneProductENSG00000197646 (Ensembl)
PI3K signalingPathwayWP4172 (WikiPathways)
PTPN11GeneProductENSG00000179295 (Ensembl)
PembrolizumabMetaboliteQ13896859 (Wikidata)
PidilizumabMetaboliteQ7191298 (Wikidata)
Ras signalingPathwayWP4223 (WikiPathways)
STAT3GeneProductENSG00000168610 (Ensembl)
TRAGeneProduct6955 (Entrez Gene)
TRBGeneProduct6957 (Entrez Gene)
TislelizumabMetaboliteD11487 (KEGG Drug)
Tumor-associated antigenGeneProduct
ZAP70GeneProductENSG00000115085 (Ensembl)

Annotated Interactions

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