Cancer Research on Prevention and Treatment    2022, Vol. 49 Issue (07) : 733-737     DOI: 10.3971/j.issn.1000-8578.2022.21.1266
Research Progress of M2-type Tumor-associated Macrophages in Lung Cancer
WAN Xiaoying1,2, ZHOU Songwen1
1. Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University, Shanghai 200433, China; 2. Medical College of Tongji University, Shanghai 200433, China
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Abstract Tumor-associated macrophages (TAMs) account for a large proportion in tumor stroma, and can be divided into M1 type (anti-tumoral) and M2 type (pro-tumoral). Recently, many experimental and clinical studies have shown that M2-type TAMs are significantly correlated with tumor stage, tumor cell differentiation, depth of invasion, angiogenesis, lymph node metastasis and therapeutic drug resistance, which eventually affects the prognosis of tumor patients. Targeted TAMs therapy is expected to benefit cancer
patients. This paper reviews the recent research of M2-type TAMs in lung cancer.
Keywords Lung cancer      Tumor-associated macrophages      Tumor microenvironment     
ZTFLH:  R734.2  
Fund:Sub-project of Key Project of Shanghai Zhangjiang High-tech Park (No. 2016-08)
Issue Date: 14 July 2022
 Cite this article:   
WAN Xiaoying,ZHOU Songwen. Research Progress of M2-type Tumor-associated Macrophages in Lung Cancer[J]. Cancer Research on Prevention and Treatment, 2022, 49(07): 733-737.
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WAN Xiaoying
ZHOU Songwen
[1] Siegel RL, Miller KD, Fuchs HE, et al. Cancer statistics, 2022[J].
CA Cancer J Clin, 2022, 72(1): 7-33.
[2] Wan X, Xie B, Sun H, et al. Exosomes derived from M2 type
tumor-associated macrophage promoteosimertinib resistance in
non-small cell lung cancer through MSTRG.292666.16-miR-
6836-5p-MAPK8IP3 axis[J]. Cancer Cell Int, 2022, 22(1): 83.
[3] Ostuni R, Kratochvill F, Murray PJ, et al. Macrophages and cancer:
from mechanisms to therapeutic implications[J]. Trends Immunol,
2015, 36(4): 229-239.
[4] Lin Y, Xu J, Lan H. Tumor-associated macrophages in tumor
metastasis: biological roles and clinical therapeutic applications[J].
J Hematol Oncol, 2019, 12(1): 76.
[5] Gü? E, Pollard JW. Redefining macrophage and neutrophil
biology in the metastatic cascade[J]. Immunity, 2021, 54(5):
[6] Cox N, Pokrovskii M, Vicario R, et al. Origins, Biology, and
Diseases of Tissue Macrophages[J]. Ann Rev Immunol, 2021, 39:
[7] Moeini P, Nied?wiedzka-Rystwej P. Tumor-Associated
Macrophages: Combination of Therapies, the Approach to
Improve Cancer Treatment[J]. Int J Mol Sci, 2021, 22(13): 7239.
[8] Locati M, Curtale G, Mantovani A. Diversity, Mechanisms, and
Significance of Macrophage Plasticity[J]. Ann Rev Pathol, 2020,
15: 123-147.
[9] Raggi F, Pelassa S, Pierobon D, et al. Regulation of Human
Macrophage M1-M2 Polarization Balance by Hypoxia and the
Triggering Receptor Expressed on Myeloid Cells-1[J]. Front
Immunol, 2017, 8: 1097.
[10] Galván-Pe?a S, O'Neill LA. Metabolic reprograming in
macrophage polarization[J]. Front Immunol, 2014, 5: 420.
[11] Pan Y, Yu Y, Wang X, et al. Tumor-Associated Macrophages in
Tumor Immunity[J]. FrontI Immunol, 2020, 11: 583084.
[12] Van Dyken SJ, Locksley RM. Interleukin-4- and interleukin 13-mediated alternatively activated macrophages: roles in
homeostasis and disease[J]. Annu Rev Immunol, 2013, 31:
[13] Jackute J, Zemaitis M, Pranys D, et al. Distribution of M1 and M2
macrophages in tumor islets and stroma in relation to prognosis of
non-small cell lung cancer[J]. BMC Immunol, 2018, 19(1): 3.
[14] Chen C, He W, Huang J, et al. LNMAT1 promotes lymphatic
metastasis of bladder cancer via CCL2 dependent macrophage
recruitment[J]. Nat Commun, 2018, 9(1): 3826.
[15] Sica A, Mantovani A. Macrophage plasticity and polarization: in
vivo veritas[J]. J Clin Invest, 2012, 122(3): 787-795.
[16] Mittal D, Gubin MM, Schreiber RD, et al. New insights
into cancer immunoediting and its three component phases--
elimination, equilibrium and escape[J]. Curr Opin Immunol, 2014,
27: 16-25.
[17] Wang N, Wang S, Wang X, et al. Research trends in
pharmacological modulation of tumor-associated macrophages[J].
Clin Transl Med, 2021, 11(1): e288.
[18] Harney AS, Arwert EN, Entenberg D, et al. Real-Time Imaging
Reveals Local, Transient Vascular Permeability, and Tumor
Cell Intravasation Stimulated by TIE2hi Macrophage-Derived
VEGFA[J]. Cancer Discov, 2015, 5(9): 932-943.
[19] Sica A, Bronte V. Altered macrophage differentiation and immune
dysfunction in tumor development[J]. J Clin Invest, 2007, 117(5):
[20] Chen L, Li J, Wang F, et al. Tie2 Expression on Macrophages Is
Required for Blood Vessel Reconstruction and Tumor Relapse
after Chemotherapy[J]. Cancer Res, 2016, 76(23): 6828-6838.
[21] Kessenbrock K, Plaks V, Werb Z. Werb, Matrix metalloproteinases:
regulators of the tumor microenvironment[J]. Cell,
2010, 141(1): 52-67.
[22] Giurisato E, Lonardi S, Telfer B, et al. Extracellular-Regulated
Protein Kinase 5-Mediated Control of p21 Expression Promotes
Macrophage Proliferation Associated with Tumor Growth and
Metastasis[J]. Cancer Res, 2020, 80(16): 3319-3330.
[23] Gil-Bernabé AM, Ferjancic S, Tlalka M, et al. Recruitment of
monocytes/macrophages by tissue factor-mediated coagulation
is essential for metastatic cell survival and premetastatic niche
establishment in mice[J]. Blood, 2012, 119(13): 3164-3175.
[24] Eisenblaetter M, Flores-Borja F, Lee JJ, et al. Visualization of
Tumor-Immune Interaction-Target-Specific Imaging of S100A8/
A9 Reveals Pre-Metastatic Niche Establishment[J]. Theranostics,
2017, 7(9): 2392-2401.
[25] Zheng Y, Wang N, Wang S, et al. XIAOPI formula inhibits the
pre-metastatic niche formation in breast cancer via suppressing
TAMs/CXCL1 signaling[J]. Cell Commun Signal, 2020, 18(1): 48.
[26] Zhang J, Li H, Wu Q, et al. Tumoral NOX4 recruits M2 tumorassociated
macrophages via ROS/PI3K signaling-dependent
various cytokine production to promote NSCLC growth[J]. Redox
Biol, 2019, 22: 101116.
[27] Guo Z, Song J, Hao J, et al. M2 macrophages promote NSCLC
metastasis by upregulating CRYAB[J]. Cell Death Dis, 2019,
10(6): 377.
[28] Lu CS, Shiau AL, Su BH, et al. Oct4 promotes M2 macrophage
polarization through upregulation of macrophage colonystimulating
factor in lung cancer[J]. J Hematol Oncol, 2020,
13(1): 62.
[29] Li Z, Feng C, Guo J, et al. GNAS-AS1/miR-4319/NECAB3
axis promotes migration and invasion of non-small cell lung
cancer cells by altering macrophage polarization[J]. Funct Integr
Genomics, 2020, 20(1): 17-28.
[30] Zhang Y, Wei Y, Jiang B, et al. Scavenger Receptor A1 Prevents
Metastasis of Non-Small Cell Lung Cancer via Suppression of
Macrophage Serum Amyloid A1[J]. Cancer Res, 2017, 77(7):
[31] Li C, Xue VW, Wang QM, et al. The Mincle/Syk/NF-κB Signaling
Circuit Is Essential for Maintaining the Protumoral Activities of
Tumor-Associated Macrophages[J]. Cancer Immunol Res, 2020,
8(8): 1004-1017.
[32] Chen XJ, Wu S, Yan RM, et al. The role of the hypoxia-Nrp-1
axis in the activation of M2-like tumor-associated macrophages in
the tumor microenvironment of cervical cancer[J]. Mol Carcinog,
2019, 58(3): 388-397.
[33] Yang L, Zhang Y. Tumor-associated macrophages: from basic
research to clinical application[J]. J Hematol Oncol, 2017, 10(1): 58.
[34] Li H, Huang N, Zhu W, et al. Modulation the crosstalk between
tumor-associated macrophages and non-small cell lung cancer to
inhibit tumor migration and invasion by ginsenoside Rh2[J]. BMC
Cancer, 2018, 18(1): 579.
[35] Hwang I, Kim JW, Ylaya K, et al. Tumor-associated macrophage,
angiogenesis and lymphangiogenesis markers predict prognosis of
non-small cell lung cancer patients[J]. J Transl Med, 2020, 18(1): 443.
[36] Mantovani A, Marchesi F, Malesci A, et al. Tumour-associated
macrophages as treatment targets in oncology[J]. Nat Rev Clin
Oncol, 2017, 14(7): 399-416.
[37] Obermajer N, Muthuswamy R, Lesnock J, et al. Positive feedback
between PGE2 and COX2 redirects the differentiation of human
dendritic cells toward stable myeloid-derived suppressor cells[J].
Blood, 2011, 118(20): 5498-5505.
[38] Schmid MC, Khan SQ, Kaneda MM, et al. Integrin CD11b
activation drives anti-tumor innate immunity[J]. Nat Commun,
2018, 9(1): 5379.
[39] T?ndell A, Subbannayya Y, Wahl SGF, et al. Analysis of Intra-
Tumoral Macrophages and T Cells in Non-Small Cell Lung
Cancer (NSCLC) Indicates a Role for Immune Checkpoint and
CD200-CD200R Interactions[J]. Cancers(Basel), 2021, 13(8):
[40] Kaneda MM, Messer KS, Ralainirina N, et al. PI3Kγ is a
molecular switch that controls immune suppression[J]. Nature,
2016, 539(7629): 437-442.
[41] La Fleur L, Botling J, He F, et al. Targeting MARCO and
IL37R on Immunosuppressive Macrophages in Lung Cancer
Blocks Regulatory T Cells and Supports Cytotoxic Lymphocyte
Function[J]. Cancer Res, 2021, 81(4): 956-967.
[42] Chen X, Gao A, Zhang F, et al. ILT4 inhibition prevents TAMand
dysfunctional T cell-mediated immunosuppression and
enhances the efficacy of anti-PD-L1 therapy in NSCLC with
EGFR activation[J]. Theranostics, 2021, 11(7): 3392-3416.
[43] Prenen H, Mazzone M. Tumor-associated macrophages: a short
compendium[J]. Cell Mol Life Sci, 2019, 76(8): 1447-1458.
[44] Huang WC, Kuo KT, Wang CH, et al. Cisplatin resistant lung
cancer cells promoted M2 polarization of tumor-associated
macrophages via the Src/CD155/MIF functional pathway[J]. J
Exp Clin Cancer Res, 2019, 38(1): 180.
[45] Liu M, Tong Z, Ding C, et al. Transcription factor c-Maf is a
checkpoint that programs macrophages in lung cancer[J]. J Clin
Invest, 2020, 130(4): 2081-2096.
[46] Li Y, Liu H, Zhao Y, et al. Tumor-associated macrophages
(TAMs)-derived osteopontin (OPN) upregulates PD-L1 expr‍ession
and predicts poor prognosis in non-small cell lung cancer
(NSCLC)[J]. Thoracic Cancer, 2021, 12(20): 2698-2709.
[47] Liu Y, Zugazagoitia J, Ahmed FS, et al. Immune Cell PD-L1
Colocalizes with Macrophages and Is Associated with Outcome
in PD-1 Pathway Blockade Therapy[J]. Clin Cancer Res, 2020,
26(4): 970-977.
[48] Gross DJ, Chintala NK, Vaghjiani RG, et al. Tumor and Tumor-
Associated Macrophage Programmed Death-Ligand 1 Expression
Is Associated With Adjuvant Chemotherapy Benefit in Lung
Adenocarcinoma[J]. J Thorac Oncol, 2022, 17(1): 89-102.
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