Interactions between Immune Cells and Tumor Cells

Wook Cho Sun

doi:10.11106/jkta.2013.6.2.96

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Sun: Interactions between Immune Cells and Tumor Cells

Original Article

J Korean Thyroid Assoc 2013;6(2):96-100.

Published online: 3 May 2013

DOI: https://doi.org/10.11106/jkta.2013.6.2.96

Interactions between Immune Cells and Tumor Cells

Wook Cho Sun

Department of Internal Medicine, Seoul National University College of Medicine, Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea

Address reprint requests to Sun Wook Cho, MD, PhD, Department of Internal Medicine, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Korea Tel: 82-2-2072-4761, Fax: 82-2-762-2292, E-mail: swchomd@snu.ac.kr

Received 10 October 2012 Accepted 6 March 2013

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http:// creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.

Keywords: Tumor microenvironment, Tumor associated macrophages (TAM), Myeloid derived suppressor cells (MDSC), Cancer immunology

References

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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.

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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