Article Figures & Data
Figures
- Figure 1
Pro-tumor functions of neutrophils. The pro-tumor functions of neutrophils can be divided into three categories depending on the sites: primary tumor site (①∼⑤); circulation (⑥); and site of metastasis (⑦, ⑧). NETs, neutrophil extracellular traps; CTCs, circulating tumor cells; ECM, extracellular matrix.
- Figure 2
Anti-tumor functions of neutrophils. The anti-tumor functions of neutrophils can be demonstrated in six ways: direct cytotoxicity to tumor cells (①, ②, ③); tumor antigen presentation (④); anti-tumor effects of NETs (⑤); and induction of apoptosis in tumor cells (⑥). MPO, myeloperoxidase; CO, carbon monoxide; ADCC, antibody-dependent cell-mediated cytotoxicity; ROS, reactive oxygen species; RNS, reactive nitrogen species; TCR, T cell receptor; NETs, neutrophil extracellular traps; TRAIL, tumor necrosis factor-related apoptosis-inducing ligand.
- Figure 3
Therapies dependent on neutrophils. Neutrophil-dependent therapies are mainly divided into six categories: blocking tumor recruitment of neutrophils; attenuating the immunosuppressive functions of neutrophils; harnessing the anti-tumor functions of neutrophils; specifically targeting the immunosuppressive neutrophils; modulating neutrophil phenotype; and targeting NETs. CXCR2, C–X–C chemokine receptor 2; CXCR4, C–X–C chemokine receptor 4; CCR5, C–C chemokine receptor 5; MMP9, matrix metalloproteinase 9; C5aR, C5a receptor; PDE5, phosphodiesterase type 5; CAR-neutrophils, chimeric antigen receptor-neutrophils; IMANs, immunomodulatory alpha neutrophils; TRAIL-R2, tumor necrosis factor-related apoptosis-inducing ligand receptor 2; FATP2, fatty acid transport protein 2; HDAC, histone deacetylase; STAT3, signal transducer and activator of transcription 3; TGF-β, transforming growth factor-β; NAMPT, nicotinamide phosphoribosyltransferase; ACE, angiotensin converting enzyme; AT1, angiotensin II type I; DNase, deoxyribonuclease; NE, neutrophil elastase; PAD4, peptidylarginine deiminase 4; CTSC, cathepsin C.
- Figure 4
Potential targets of neutrophils identified by single-cell RNA sequencing (scRNA-seq). There are two main potential strategies: Enhancing anti-tumor functions of neutrophils with high ISG expression by targeting IRF1 and Attenuating pro-tumor functions of neutrophils with high VEGFA, LDHA, BHLHE40, CCL4, SPP1, and PD-L1 expression by targeting BHLHE40. ISG, IFN-stimulated genes; IRF1, interferon-responsive transcription factor 1; VEGFA, vascular endothelial growth factor A; LDHA, lactate dehydrogenase A; BHLHE40, basic helix-loop-helix transcription factor 40; CCL4, C-C chemokine ligand 4; SPP1, phosphoprotein 1; PD-L1, programmed cell death ligand-1.
Tables
Drug Phase Disease Trial identifier Study status CXCR2/IL-8 antagonists AZD5069 I/II Squamous cell carcinoma of head and neck NCT02499328 Active, not recruiting I/II PDAC NCT02583477 Completed I/II Metastatic castrate-resistant prostate cancer NCT03177187 Terminated BMS-986253 I/II Hormone-sensitive prostate cancer NCT03689699 Active, not recruiting I/II HCC NCT04050462 Active, not recruiting I HCC, NSCLC NCT04123379 Recruiting I/II Metastatic or unresectable solid tumours NCT03400332 Recruiting I Metastatic solid tumours NCT04572451 Recruiting SX-682 I Metastatic melanoma NCT03161431 Recruiting I PDAC NCT04477343 Recruiting I Myelodysplastic syndrome NCT04245397 Recruiting Navarixin/MK-7123 II Advanced/metastatic solid tumors NCT03473925 Completed Reparixin II Breast cancer NCT02370238 Completed I Breast cancer NCT02001974 Completed C/EBPα MTL-CEBPA small activating RNA I HCC NCT02716012 Unknown status I Solid tumors NCT04105335 Active, not recruiting TGF-β pathway inhibitors Galunisertib II Glioblastoma NCT01582269 Active, not recruiting I Glioma NCT01682187 Active, not recruiting I Ovarian carcinosarcoma NCT03206177 Unknown status I Breast cancer NCT02672475 Active, not recruiting II Metastatic castration-resistant prostate cancer NCT02452008 Recruiting II Rectal cancer NCT02688712 Active, not recruiting II Nasopharyngeal carcinoma NCT04605562 Not yet recruiting I HCC NCT02240433 Completed II HCC NCT01246986 Completed I/II HCC, Solid tumors and NSCLC NCT02423343 Completed I PDAC NCT02734160 Completed Fresolimumab (GC1008) I/II NSCLC NCT02581787 Completed IMC-TR1 I Neoplasms NCT01646203 Completed STAT3 inhibitors Napabucasin III Colorectal cancer NCT02753127 Completed I HCC NCT02358395 Completed I/II HCC NCT02279719 Completed TTI101 I HCC NCT03195699 Active, not recruiting Danvatirsen I HCC NCT01839604 Completed Lcaritin I HCC NCT02496949 Completed II HCC NCT01972672 Completed III HCC NCT03236636 Unknown status III HCC NCT03236649 Terminated TRAIL receptor 2 agonists Tigatuzumab II Breast cancer NCT01307891 Completed II HCC NCT01033240 Completed CS-1008 I Colorectal neoplasms NCT01220999 Completed DS8273a I Solid tumors and lymphoma NCT02076451 Completed I Colorectal cancer NCT02991196 Terminated I Melanoma NCT02983006 Completed CD47-SIRPα pathway inhibitors Hu5F9-G4 I Solid tumors NCT02216409 Completed IBI188 I Advanced malignancies NCT03717103 Completed CC-90002 I Hematologic neoplasms NCT02367196 Completed Magrolimab I/II Colorectal cancer NCT02953782 Completed TTI621 I Solid tumors NCT02890368 Terminated AO176 I Solid tumors NCT03834948 Completed BI765063 I Solid tumors NCT03990233 Active, not recruiting Recombinant arginase 1/arginase 1 inhibitors Pegzilarginase I/II Extensive disease small cell lung cancer NCT03371979 Completed INCB001158 I/II Advanced/Metastatic solid tumors NCT02903914 Completed I/II Solid tumors NCT03314935 Completed Anti-C5aR IPH5401 I Advanced solid tumors NCT03665129 Terminated PDE5 inhibitors Tadalafil I Liver dominant colorectal cancer or PDAC NCT03785210 Completed II Head and neck cancers NCT02544880 Completed Sildenafil II/ III NSCLC NCT00752115 Completed HDAC inhibitors Resminostat II HCC NCT00943449 Completed Belinostat I/II HCC NCT00321594 Completed CCR5 inhibitor Maraviroc I Colorectal cancer NCT03274804 Completed I Colorectal cancer NCT01736813 Completed CXCR4 inhibitor Plerixafor I PDAC, colorectal and ovarian cancer NCT02179970 Completed NAMPT inhibitor Daporinad II Cutaneous T cell lymphoma NCT00431912 Completed MMP9 inhibitor Andecaliximab III Gastric adenocarcinoma NCT02545504 Completed NETs inhibitors Pulmozyme (rhDNase) I Head and neck cancers NCT00536952 Unknown status Oshadi D II Acute myeloid/lymphoid leukemia NCT02462265 Suspended PDAC, pancreatic ductal adenocarcinoma; HCC, hepatocellular carcinoma; NSCLC, non-small cell lung cancer.
In this issue
Jump to section
Related Articles
Cited By...
- No citing articles found.