Copyright ©The Author(s) 2021.
World J Clin Cases. Dec 6, 2021; 9(34): 10438-10450
Published online Dec 6, 2021. doi: 10.12998/wjcc.v9.i34.10438
Table 1 The mechanisms of immune escape in different digestive tumours
HLA-GBespalova et al[8], 2020; Liu et al[16], 2020CRCNK cells, T lymphocytes, and antigen-presenting cellsUpILT-2, ILt-4, and KIR2DL4By directly binding to the inhibitory receptors ILT-2, ILt-4, and KIR2DL4, leading to apoptosis of NK and T cells and weakening host immune defences
HLA-IZhao et al[11], 2011; Li et al[12], 2010; Özgül Özdemir et al[19], 2016Oesophageal malignant tumour, CRCCD8+ T cells, T lymphocytesDownTAADownregulates the expression of HLA-I and reduces the expression of tumour-associated antigen (TAA) on the surface of tumour cells, evading recognition and attack by immune cells
HLA-EHuang et al[17], 2017; Abd Hamid et al[18], 2019Early CRCCTLs and NK cellsUpCD94/NKG2AHLA-E is overexpressed on the surface of early CRC cells and can bind to the HLA-E receptor CD94/NKG2A, which is expressed on the surface of CTLs and NK cells, thus inhibiting their activity
PD-L1Calderaro et al[27], 2016Oesophageal carcinomaEGFRUpPI3K/AKT, EGFR-RAS-RAF-ERKBinding of the transmembrane protein - programmed death-ligand 1 (PD-L1) expressed in tumour cells or cells in the TME to PD-1 expressed on T cells can induce the production of immunosuppressive signals and decrease the proliferation of T cells, resulting in the depletion of T cells
Liu et al[30], 2020CRCCCL5Upp65/STAT3-CSN5-PD-L1Stabilizes PD-L1 in and out of cells through the p65/STAT3-CSN5-PD-L1 pathway mediated by NF-κB1 p65 (p65), which inhibits T-cell-mediated killing of HT29 tumour cells
Ghedini et al[31], 2018CRCFGFR2UpJAK/STAT3The tyrosine kinase domain initiates a series of intracellular signal cascade reactions, activates the JAK/STAT3 signalling pathway, and induces PD-L1 expression in CRC cells, thus participating in the occurrence and development of CRC
Li et al[34], 2019CRCCXCL5UpPIK3/AktThe binding of CXCL5 to CXCR2 on the surface of CRC cells promotes the movement of the CXCL5-CXCR2 axis, thus activating the PI3K/AKT signalling pathway and upregulating the expression of PD-L1 in CRC
Li et al[38], 2019Gallbladder malignant tumourT cellsUpPIK3/AktUpregulation of PD-L1 in gallbladder malignant tumour cells, activated the PIK3/Akt pathway, inhibited the cytotoxicity mediated by normal T cells, and promoted tumour growth and development
Galectin-9Wang et al[41], 2016; Halama et al[43], 2011Oesophageal carcinoma, CRCNK cellsDownRho/ROCK-1, F-actin polarizationThe low expression of Galectin-9 may lead to decreased activation or insufficient transport of NK cells to the tumour site
DKK2Xiao et al[44], 2018CRCNK cells, CD8+ T cellsUpSTATThe binding of DKK2 to LRP5 on the surface of NK cells leads to the disordering of STAT5 nuclear localization in NK cells and hinders the activation of NK cells
MDSCsGeiger et al[53], 2016CRCT cellsUpL-arginine The high expression of MDSCs consumes a large quantity of L-arginine, and the resulting depletion of L-arginine affects T-cell proliferation
Li et al[54], 2018Oesophageal carcinomaT cellsUpAkt1/rela/IL8 Oesophageal malignant tumour cells can guide MDSCs to migrate to the tumour site and promote tumour progression by activating the Akt1/rela/IL8 signalling pathway
Treg cellsChen et al[60], 2017CRCTCRUpCXCL13-CXCR5 axisHDCC mainly promotes the infiltration of Treg cells by binding to CXCR5 on the surface of Treg cells by secreting CXCL13, which initiates the CXCL13-CXCR5 axis, promotes the proliferation of Treg cells and the aggregation of Treg cells at the tumour site
TIM-3Shan et al[72], 2016Oesophageal carcinomaCD4+ Th1, CD8+ T cells, dysfunctional CD8+ T cells and FoxP3+ Treg cellsUpAKT/GSK-3 β/SnailA high expression of TIM-3 in tumour cells often indicates a poor prognosis of tumours
CD47Fujiwara-Tani et al[76], 2019Gastric tumour, CRCMacrophagesUpSirp αCD47 can prevent macrophage-mediated phagocytosis and antigen presentation by interacting with the receptor Sirp α expressed on macrophages, thus allowing tumour cells to escape the immune surveillance of macrophages
NF-κBOuyang et al[83], 2021; He et al[84], 2021Gallbladder malignant tumours, Pancreatic malignant tumours, CRCT cell granzyme B geneUpToll-like receptor 4, NF- κB/p65NF-κB realizes the immune escape of tumour cells by affecting the transcription of effector T cells at the cellular transcriptional level. NF-κB inhibits GZMB transcription in T cells, induces CTL dysfunction, and promotes tumour immune escape
IDO1+ Paneth cellsMezrich et al[90], 2010Oesophageal carcinoma, CRCCD8+ T cellsUpCanine uric acid, tryptophanIDO facilitates immune escape by locally increasing the level of canine uric acid derived from tumour epithelial cells and consuming tryptophan. The increased level of canine uric acid promotes the differentiation of Treg cells through the aromatic hydrocarbon receptor AhR29, and the depletion of tryptophan can lead to cell cycle arrest of T cells, both of which can inhibit the antitumour immune response