TABLE 3.
Factors implicated in the expansion and recruitment of MDSCs in GI cancer
| Target | Cancer Model | Source | Mechanism | Reference a |
|---|---|---|---|---|
| IL‐10 | CRC | Tumor microenvironment and spleen | IL‐10 deficiency increases MDSCs accumulation in the spleen and tumor. | Tanikawa et al., 2012. [189] |
| CEACAM1 | CRC | Liver | Ceacam1 deficiency diminished CD11b+Gr1+MDSCs recruitment to the metastatic liver. | Arabzadeh et al., 2013. [190] |
| IL‐6 | ESCC | Peripheral blood | MDSCs recruitment was associated with invasive esophageal tumors and with increased IL‐6 levels. | Chen et al., 2014. [125] |
| CD38 | EC | Spleen | CD38 could promote monocytic MDSCs population expansion and regulate iNOS expression. | Karakashera et al., 2015. [24] |
| CCL2 | CRC | Colon adenocarcinoma tissue | CCL2 regulates G‐MDSC accumulation and T‐cell suppressive activity via STAT3. | Chun et al., 2015. [191] |
| CD40 | GC | Spleen and tumor tissue | CD40 expression upregulates the chemokine receptor CXCR5 and promotes MDSCs migration and accumulation. | Ding et al., 2015. [192] |
| G‐CSF | CAC | Colon tissues | G‐CSF could promote MDSCs survival and activation through the STAT3 signaling pathway. | Li et al., 2016. [62] |
| CCL15 | CRC | Tumor tissue | CCL15‐CCR1+ axis promotes MDSCs accumulation in the tumor microenvironment. | Inamoto et al., 2016. [114] |
| S1pr3 | CRC | Peripheral blood, spleen and bone marrow | GM‐CSF promotes MDSCs via S1pr3 through Rho kinase and the extracellular signal‐regulated kinase‐dependent pathway. | Li et al., 2017. [193] |
| STAT6 | Intestinal tumorigenesis | Spleen and lamina propria | STAT6 promoted expansion of MDSCs in the spleen and lamina propria of ApcMin/+ mice, implying regulation of antitumor T‐cell response. | Jayakumar et al., 2017. [194] |
| VEGF‐A/CXCL1 | CRC | Liver | VEGF‐A ‐CXCL1‐CXCR2 recruits MDSCs to form a pre‐metastatic niche. | Wang et al., 2017. [109] |
| GM‐CSF | CRC | Colon tissues | GM‐CSF was sufficient to differentiate hematopoietic precursors into MDSCs. | Ma et al., 2017. [195] |
| CCR5 | GC | Periphery and tumor | CCL5‐CCR5 axis recruits MDSCs, and blocks CCR5 to reduce the accumulation of MDSCs and enhances anti‐PD1 efficacy. | Yang et al., 2018. [196] |
| Acid ceramidase | CAC | Tumor tissue | Acid ceramidase protects from tumor incidence in colitis‐associated cancer and inhibits the expansion of neutrophils and G‐MDSC in the tumor microenvironment. | Espaillat et al., 2018. [197] |
| RIPK3 | CRC | Colorectal tumor tissues | In MDSCs, PGE2 suppressed RIPK3 expression and enhanced NF‐κB and COX‐2 expression, which catalyzed PGE2 synthesis. | Yan et al., 2018. [198] |
| CXCL4 | CRC | Tumor tissues and peritoneal cavity | Surgical trauma contributes to colon cancer progression by downregulating CXCL4 and hence promoting MDSCs recruitment, which leads to an immunosuppressive environment. | Xu et al., 2018. [199] |
| CXCR4 | CAC | Colon tissue | CXCR4 overexpression promotes the infiltration of bone marrow‐derived MDSCs. | Yu et al., 2019. [200] |
| DCHLL | CRC | Tumor, blood and bone marrow | Blocking DC‐HIL function is a potentially useful treatment for at least colorectal cancer with high blood levels of DC‐HIL+MDSCs. | Kobayashi et al., 2019. [164] |
| STAT3 | HCC | Liver | Inhibition of STAT3, p‐STAT3, upregulation of the pro‐apoptotic proteins Bax, cleaved caspase‐3, and downregulation of the anti‐apoptotic protein Bcl‐2. | Guha et al., 2019. [201] |
| PAR2 | CAC | Tumor tissue | Absence of PAR2 in MDSCs directly enhanced their immunosuppressive activity by promoting STAT3‐mediated ROS production. | Ke et al., 2020. [202] |
Information listed in the table are arranged in ascending chronological order.
Abbreviations: GI cancer, gastrointestinal cancer; MDSCs, myeloid‐derived suppressor cells; G‐MDSCs, granulocytic MDSCs; CRC, colorectal cancer; GC, gastric cancer; HCC, hepatocellular carcinoma; ESCC, esophageal squamous cell carcinoma; CAC, colitis‐associated colorectal cancer; IL‐10, interleukin 10; CEACAM1, carcinoembryonic antigen‐related cell adhesion molecule 1;IL‐6, interleukin 6; iNOS, inducible nitric oxide synthase; CCL2, C–C motif chemokine ligand 2; STAT3, signal transducer and activator of transcription 3; CXCR5, C–X–C chemokine receptor 5; G‐CSF, granulocyte colony‐stimulating factor;CCL15, C–C motif chemokine ligand 15; CCR1, C–C motif chemokine receptor 1; S1pr3, S1P receptor 3; GM‐CSF, granulocyte macrophage colony‐stimulating factor; STAT6, signal transducer and activator of transcription 6; VEGFA, vascular endothelial growth factor A; CXCL1, C–X–C motif chemokine ligand 1; CXCR2, C–X–C motif chemokine receptor 2; GM‐CSF, granulocyte macrophage colony‐stimulating factor;CCR5, C–C motif chemokine receptor 5; RIPK3, receptor‐interacting protein kinase 3; PGE2, prostaglandin E2; NF‐κB, nuclear factor kappa‐B; COX‐2, cyclooxygenase‐2; CXCL4, C–X–C motif chemokine ligand 4; CXCR4, C–X–C motif chemokine receptor 4; DC‐HIL, dendritic cell‐associated heparan sulfate proteoglycan‐dependent integrin ligand; Bax, Bcl‐2‐associated X; Bcl‐2, B‐cell lymphoma‐2; PAR2, protease activated receptor 2.