Journal List > J Korean Thyroid Assoc > v.6(2) > 1056549

Sun: Interactions between Immune Cells and Tumor Cells

Abstract

Tumor microenvironment is defined as a heterogeneous complex composed of cancer cells, vascular endothelial cells, fibroblasts, and diverse immune cells. Cancer immunology is the study of interactions between the immune system and cancer cells which is applied to develop therapeutic strategies for human cancers. This review focused on tumor promoting myeloid derived cells such as tumor associated macrophages (TAM) and myeloid derived suppressor cells (MDSC) and their therapeutic applications.

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Fig. 1.
Macrophage activation and polarization. “Classically activated” M1 macrophages are activated by TNF, IFN γ or bacterial products such as microbial lipopolysaccharide (LPS), express high levels of IL12, IL–23, TNF, IL–1 or CXCL10 and low levels of IL10. By contrast, “alternatively activated” M2 macrophages are activated by IL4, IL10, IL13, M–CSF or glucocorticoid hormones, express high levels of IL10, IL–13, IL–4, CCL2, scavenger receptor-A or mannose receptor and low levels of IL12. Functionally, M1 macrophages are microbicidal or tumoricidal and M2 macrophages play a role in cell clearance/wound healing or tumor promotions.
jkta-6-96f1.tif
Table 1.
Therapeutic strategies to target TAMs
Therapeutic agents Study subjects References
Blocking the differentiation and recruitment of macrophages
C–fms inhibitor
Yondelis
Anti–CCL2 blocking antibody
CNTO 888
MLN1202
COX inhibitor, DFU
Killing of macrophages in the tumor microenvironment
Clonodrate–loaded liposomes (CLIPs)
Zoledronic acid
Repolarization of TAMs
Proton pump inhibitor pantoprazole
IL–12
NF–κb signaling inhibitor
Histidine-rich glycoprotein (HRG)
Inhibition of M2 macrophage functions
Prednisolone liposomes
Silibinin
Rituximab (anti–CD20 Ab)
Human
Mice
Human
Human
Mice
Mice
Human
Mice
Mice
Mice
Mice
Human
Human
NCT01004861
NCT01316822
NCT01346358
19,20)
NCT00992186
NCT01204996
NCT01015560
21-23)
24-26)
27)
NCT01163903
28,29)
30)
31)
32)
NCT01129570
33)

NCT: clinical trial registry numbers in ClinicalTrials.gov, DFU: 5,5-dimethyl–3–(3–fluorophenyl)–4–(4–methylsulphonyl)phenyl–2(5H)–furanone, TAMs: tumor–associated macrophages

Table 2.
Therapeutic strategies to target MDSCs
Therapeutic agents Type of cancer Study subjects References
Vitamin D3 Head &neck cancer Human 15)
All-trans retinoic acid Sarcoma, colon cancer, Human, mice 13,14)
metastatic renal cell carcinoma   34)
KIT-specific antibody Colon cancer Mice
VEGF-trap Solid tumor   35)
VEGF-specific antibody (avastin) Metastatic renal cell carcinoma Human 36)
Cyclooxygenase 2 inhibitor (SC58236) Mammary carcinoma Mice 37)
Bisphosphonate, sildenafil Mammary carcinoma, colon cancer Mice 38)
Amino-bisphosphonate Mammary tumors Mice 39)
Gemcitabine Mammary tumors, lung cancer Mice 40,41)
Nitroaspirin Colon cancer Mice 42)

MDSCs: myeloid derived suppressor cells

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