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Published in: BMC Immunology 1/2018

Open Access 01-12-2018 | Research article

Distribution of M1 and M2 macrophages in tumor islets and stroma in relation to prognosis of non-small cell lung cancer

Authors: Jurgita Jackute, Marius Zemaitis, Darius Pranys, Brigita Sitkauskiene, Skaidrius Miliauskas, Simona Vaitkiene, Raimundas Sakalauskas

Published in: BMC Immunology | Issue 1/2018

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Abstract

Background

Non-small cell lung cancer (NSCLC) remains the most common cause of cancer related death worldwide. Tumor-infiltrating macrophages are believed to play an important role in growth, progression, and metastasis of tumors. In NSCLC, the role of macrophages remains controversial; therefore, we aimed to evaluate the distribution of macrophages (M1 and M2) in tumor islets and stroma and to analyze their relations to patients’ survival.

Methods

Lung tissue specimens from 80 NSCLC patients who underwent surgical resection for NSCLC (pathological stage I-III) and 16 control group subjects who underwent surgery because of recurrent spontaneous pneumothorax were analyzed. Immunohistochemical double staining of CD68/iNOS (markers for M1 macrophages) and CD68/CD163 (markers for M2 macrophages) was performed and evaluated in a blinded manner. The numbers of M1 and M2 macrophages in tumor islets and stroma were counted manually.

Results

Predominant infiltration of M1 and M2 macrophages was observed in the tumor stroma compared with the tumor islets. M2 macrophages predominated over M1 macrophages in the tumor tissue. Tumor islets-infiltrating M1 macrophages and the number of total tumor-infiltrating M2 macrophages were independent predictors of patients survival: high infiltration of M1 macrophages in tumor islets was associated with increased overall survival in NSCLC (P < 0.05); high infiltration of total M2 macrophages in tumor (islets and stroma) was associated with reduced overall survival in NSCLC (P < 0.05).

Conclusions

This study demonstrated that high infiltration of M1 macrophages in the tumor islets and low infiltration of total tumor-infiltrating M2 macrophages were associated with improved NSCLC patients’ survival.

Trial registration

ClinicalTrials.​gov NCT01955343, registered on September 27, 2013
Literature
1.
go back to reference Pollard JW. Tumour-educated macrophages promote tumour progression and metastasis. Nat Rev Cancer. 2004;4(1):71–8.CrossRefPubMed Pollard JW. Tumour-educated macrophages promote tumour progression and metastasis. Nat Rev Cancer. 2004;4(1):71–8.CrossRefPubMed
2.
go back to reference Lin A, et al. Dendritic cells integrate signals from the tumor microenvironment to modulate immunity and tumor growth. Immunol Lett. 2010;127(2):77–84.CrossRefPubMed Lin A, et al. Dendritic cells integrate signals from the tumor microenvironment to modulate immunity and tumor growth. Immunol Lett. 2010;127(2):77–84.CrossRefPubMed
3.
go back to reference Chen JJ, et al. Tumor-associated macrophages: the double-edged sword in cancer progression. J Clin Oncol. 2005;23(5):953–64.CrossRefPubMed Chen JJ, et al. Tumor-associated macrophages: the double-edged sword in cancer progression. J Clin Oncol. 2005;23(5):953–64.CrossRefPubMed
4.
go back to reference Loose D, Van de Wiele C. The immune system and cancer. Cancer Biother Radiopharm. 2009;24(3):369–76.CrossRefPubMed Loose D, Van de Wiele C. The immune system and cancer. Cancer Biother Radiopharm. 2009;24(3):369–76.CrossRefPubMed
6.
go back to reference Lewis CE, Pollard JW. Distinct role of macrophages in different tumor microenvironments. Cancer Res. 2006;66(2):605–12.CrossRefPubMed Lewis CE, Pollard JW. Distinct role of macrophages in different tumor microenvironments. Cancer Res. 2006;66(2):605–12.CrossRefPubMed
8.
go back to reference Medrek C, et al. The presence of tumor associated macrophages in tumor stroma as a prognostic marker for breast cancer patients. BMC Cancer. 2012;12:306.CrossRefPubMedPubMedCentral Medrek C, et al. The presence of tumor associated macrophages in tumor stroma as a prognostic marker for breast cancer patients. BMC Cancer. 2012;12:306.CrossRefPubMedPubMedCentral
9.
go back to reference Mantovani A, et al. Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Trends Immunol. 2002;23(11):549–55.CrossRefPubMed Mantovani A, et al. Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Trends Immunol. 2002;23(11):549–55.CrossRefPubMed
10.
go back to reference Ong SM, et al. Macrophages in human colorectal cancer are pro-inflammatory and prime T cells towards an anti-tumour type-1 inflammatory response. Eur J Immunol. 2012;42(1):89–100.CrossRefPubMed Ong SM, et al. Macrophages in human colorectal cancer are pro-inflammatory and prime T cells towards an anti-tumour type-1 inflammatory response. Eur J Immunol. 2012;42(1):89–100.CrossRefPubMed
11.
go back to reference Dumont P, et al. Expression of galectin-3 in the tumor immune response in colon cancer. Lab Investig. 2008;88(8):896–906.CrossRefPubMed Dumont P, et al. Expression of galectin-3 in the tumor immune response in colon cancer. Lab Investig. 2008;88(8):896–906.CrossRefPubMed
13.
go back to reference Miotto D, et al. CD8+ T cells expressing IL-10 are associated with a favourable prognosis in lung cancer. Lung Cancer. 2010;69(3):355–60.CrossRefPubMed Miotto D, et al. CD8+ T cells expressing IL-10 are associated with a favourable prognosis in lung cancer. Lung Cancer. 2010;69(3):355–60.CrossRefPubMed
14.
go back to reference Lopez MV, et al. IL-12 and IL-10 expression synergize to induce the immune-mediated eradication of established colon and mammary tumors and lung metastasis. J Immunol. 2005;175(9):5885–94.CrossRefPubMed Lopez MV, et al. IL-12 and IL-10 expression synergize to induce the immune-mediated eradication of established colon and mammary tumors and lung metastasis. J Immunol. 2005;175(9):5885–94.CrossRefPubMed
15.
go back to reference Mocellin S, Marincola FM, Young HA. Interleukin-10 and the immune response against cancer: a counterpoint. J Leukoc Biol. 2005;78(5):1043–51.CrossRefPubMed Mocellin S, Marincola FM, Young HA. Interleukin-10 and the immune response against cancer: a counterpoint. J Leukoc Biol. 2005;78(5):1043–51.CrossRefPubMed
16.
go back to reference Hayakawa Y, et al. IFN-gamma-mediated inhibition of tumor angiogenesis by natural killer T-cell ligand, alpha-galactosylceramide. Blood. 2002;100(5):1728–33.PubMed Hayakawa Y, et al. IFN-gamma-mediated inhibition of tumor angiogenesis by natural killer T-cell ligand, alpha-galactosylceramide. Blood. 2002;100(5):1728–33.PubMed
17.
18.
go back to reference Wang B, et al. Expression of tumor necrosis factor-alpha-mediated genes predicts recurrence-free survival in lung cancer. PLoS One. 2014;9(12):e115945.CrossRefPubMedPubMedCentral Wang B, et al. Expression of tumor necrosis factor-alpha-mediated genes predicts recurrence-free survival in lung cancer. PLoS One. 2014;9(12):e115945.CrossRefPubMedPubMedCentral
21.
go back to reference Chansky K, et al. The International Association for the Study of Lung Cancer staging project: prognostic factors and pathologic TNM stage in surgically managed non-small cell lung cancer. J Thorac Oncol. 2009;4(7):792–801.CrossRefPubMed Chansky K, et al. The International Association for the Study of Lung Cancer staging project: prognostic factors and pathologic TNM stage in surgically managed non-small cell lung cancer. J Thorac Oncol. 2009;4(7):792–801.CrossRefPubMed
22.
go back to reference Rabe KF, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med. 2007;176(6):532–55.CrossRefPubMed Rabe KF, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med. 2007;176(6):532–55.CrossRefPubMed
24.
go back to reference Kawai O, et al. Predominant infiltration of macrophages and CD8(+) T cells in cancer nests is a significant predictor of survival in stage IV nonsmall cell lung cancer. Cancer. 2008;113(6):1387–95.CrossRefPubMed Kawai O, et al. Predominant infiltration of macrophages and CD8(+) T cells in cancer nests is a significant predictor of survival in stage IV nonsmall cell lung cancer. Cancer. 2008;113(6):1387–95.CrossRefPubMed
25.
go back to reference Sickert D, et al. Characterization of macrophage subpopulations in colon cancer using tissue microarrays. Histopathology. 2005;46(5):515–21.CrossRefPubMed Sickert D, et al. Characterization of macrophage subpopulations in colon cancer using tissue microarrays. Histopathology. 2005;46(5):515–21.CrossRefPubMed
26.
go back to reference Sica A, et al. Origin and functions of tumor-associated myeloid cells (TAMCs). Cancer Microenviron. 2012;5(2):133–49.CrossRefPubMed Sica A, et al. Origin and functions of tumor-associated myeloid cells (TAMCs). Cancer Microenviron. 2012;5(2):133–49.CrossRefPubMed
27.
go back to reference Richards DM, Hettinger J, Feuerer M. Monocytes and macrophages in cancer: development and functions. Cancer Microenviron. 2013;6(2):179–91.CrossRefPubMed Richards DM, Hettinger J, Feuerer M. Monocytes and macrophages in cancer: development and functions. Cancer Microenviron. 2013;6(2):179–91.CrossRefPubMed
28.
go back to reference Mueller MM, Fusenig NE. Friends or foes - bipolar effects of the tumour stroma in cancer. Nat Rev Cancer. 2004;4(11):839–49.CrossRefPubMed Mueller MM, Fusenig NE. Friends or foes - bipolar effects of the tumour stroma in cancer. Nat Rev Cancer. 2004;4(11):839–49.CrossRefPubMed
29.
go back to reference Welsh TJ, et al. Macrophage and mast-cell invasion of tumor cell islets confers a marked survival advantage in non-small-cell lung cancer. J Clin Oncol. 2005;23(35):8959–67.CrossRefPubMed Welsh TJ, et al. Macrophage and mast-cell invasion of tumor cell islets confers a marked survival advantage in non-small-cell lung cancer. J Clin Oncol. 2005;23(35):8959–67.CrossRefPubMed
30.
go back to reference Al-Shibli K, et al. The prognostic value of intraepithelial and stromal innate immune system cells in non-small cell lung carcinoma. Histopathology. 2009;55(3):301–12.CrossRefPubMed Al-Shibli K, et al. The prognostic value of intraepithelial and stromal innate immune system cells in non-small cell lung carcinoma. Histopathology. 2009;55(3):301–12.CrossRefPubMed
31.
go back to reference Ma J, et al. The M1 form of tumor-associated macrophages in non-small cell lung cancer is positively associated with survival time. BMC Cancer. 2010;10:112.CrossRefPubMedPubMedCentral Ma J, et al. The M1 form of tumor-associated macrophages in non-small cell lung cancer is positively associated with survival time. BMC Cancer. 2010;10:112.CrossRefPubMedPubMedCentral
32.
go back to reference Zhang B, et al. M2-polarized tumor-associated macrophages are associated with poor prognoses resulting from accelerated lymphangiogenesis in lung adenocarcinoma. Clinics (Sao Paulo). 2011;66(11):1879–86.CrossRef Zhang B, et al. M2-polarized tumor-associated macrophages are associated with poor prognoses resulting from accelerated lymphangiogenesis in lung adenocarcinoma. Clinics (Sao Paulo). 2011;66(11):1879–86.CrossRef
34.
go back to reference Casazza A, et al. Tumor stroma: a complexity dictated by the hypoxic tumor microenvironment. Oncogene. 2014;33(14):1743–54.CrossRefPubMed Casazza A, et al. Tumor stroma: a complexity dictated by the hypoxic tumor microenvironment. Oncogene. 2014;33(14):1743–54.CrossRefPubMed
35.
go back to reference Carus A, et al. Tumor-associated neutrophils and macrophages in non-small cell lung cancer: no immediate impact on patient outcome. Lung Cancer. 2013;81(1):130–7.CrossRefPubMed Carus A, et al. Tumor-associated neutrophils and macrophages in non-small cell lung cancer: no immediate impact on patient outcome. Lung Cancer. 2013;81(1):130–7.CrossRefPubMed
36.
go back to reference Allavena P, et al. The inflammatory micro-environment in tumor progression: the role of tumor-associated macrophages. Crit Rev Oncol Hematol. 2008;66(1):1–9.CrossRefPubMed Allavena P, et al. The inflammatory micro-environment in tumor progression: the role of tumor-associated macrophages. Crit Rev Oncol Hematol. 2008;66(1):1–9.CrossRefPubMed
37.
go back to reference Curtis JL, Freeman CM, Hogg JC. The immunopathogenesis of chronic obstructive pulmonary disease: insights from recent research. Proc Am Thorac Soc. 2007;4(7):512–21.CrossRefPubMedPubMedCentral Curtis JL, Freeman CM, Hogg JC. The immunopathogenesis of chronic obstructive pulmonary disease: insights from recent research. Proc Am Thorac Soc. 2007;4(7):512–21.CrossRefPubMedPubMedCentral
38.
go back to reference Jackute J, et al. Distribution of CD4(+) and CD8(+) T cells in tumor islets and stroma from patients with non-small cell lung cancer in association with COPD and smoking. Medicina (Kaunas). 2015;51(5):263–71.CrossRef Jackute J, et al. Distribution of CD4(+) and CD8(+) T cells in tumor islets and stroma from patients with non-small cell lung cancer in association with COPD and smoking. Medicina (Kaunas). 2015;51(5):263–71.CrossRef
39.
go back to reference Mehta H, Nazzal K, Sadikot RT. Cigarette smoking and innate immunity. Inflamm Res. 2008;57(11):497–503.CrossRefPubMed Mehta H, Nazzal K, Sadikot RT. Cigarette smoking and innate immunity. Inflamm Res. 2008;57(11):497–503.CrossRefPubMed
40.
go back to reference Ueno T, et al. Significance of macrophage chemoattractant protein-1 in macrophage recruitment, angiogenesis, and survival in human breast cancer. Clin Cancer Res. 2000;6(8):3282–9.PubMed Ueno T, et al. Significance of macrophage chemoattractant protein-1 in macrophage recruitment, angiogenesis, and survival in human breast cancer. Clin Cancer Res. 2000;6(8):3282–9.PubMed
41.
go back to reference Jensen TO, et al. Macrophage markers in serum and tumor have prognostic impact in American joint committee on cancer stage I/II melanoma. J Clin Oncol. 2009;27(20):3330–7.CrossRefPubMed Jensen TO, et al. Macrophage markers in serum and tumor have prognostic impact in American joint committee on cancer stage I/II melanoma. J Clin Oncol. 2009;27(20):3330–7.CrossRefPubMed
42.
go back to reference Hashimoto I, et al. Macrophage infiltration and angiogenesis in endometrial cancer. Anticancer Res. 2000;20(6C):4853–6.PubMed Hashimoto I, et al. Macrophage infiltration and angiogenesis in endometrial cancer. Anticancer Res. 2000;20(6C):4853–6.PubMed
43.
go back to reference Koga J, et al. Angiogenesis and macrophage infiltration in Borrmann type IV gastric cancer. Fukuoka Igaku Zasshi. 2001;92(9):334–9.PubMed Koga J, et al. Angiogenesis and macrophage infiltration in Borrmann type IV gastric cancer. Fukuoka Igaku Zasshi. 2001;92(9):334–9.PubMed
44.
go back to reference Forssell J, et al. High macrophage infiltration along the tumor front correlates with improved survival in colon cancer. Clin Cancer Res. 2007;13(5):1472–9.CrossRefPubMed Forssell J, et al. High macrophage infiltration along the tumor front correlates with improved survival in colon cancer. Clin Cancer Res. 2007;13(5):1472–9.CrossRefPubMed
45.
46.
go back to reference Shimura S, et al. Reduced infiltration of tumor-associated macrophages in human prostate cancer: association with cancer progression. Cancer Res. 2000;60(20):5857–61.PubMed Shimura S, et al. Reduced infiltration of tumor-associated macrophages in human prostate cancer: association with cancer progression. Cancer Res. 2000;60(20):5857–61.PubMed
47.
go back to reference Chen JJ, et al. Up-regulation of tumor interleukin-8 expression by infiltrating macrophages: its correlation with tumor angiogenesis and patient survival in non-small cell lung cancer. Clin Cancer Res. 2003;9(2):729–37.PubMed Chen JJ, et al. Up-regulation of tumor interleukin-8 expression by infiltrating macrophages: its correlation with tumor angiogenesis and patient survival in non-small cell lung cancer. Clin Cancer Res. 2003;9(2):729–37.PubMed
48.
go back to reference Toomey D, et al. Infiltrating immune cells, but not tumour cells, express FasL in non-small cell lung cancer: no association with prognosis identified in 3-year follow-up. Int J Cancer. 2003;103(3):408–12.CrossRefPubMed Toomey D, et al. Infiltrating immune cells, but not tumour cells, express FasL in non-small cell lung cancer: no association with prognosis identified in 3-year follow-up. Int J Cancer. 2003;103(3):408–12.CrossRefPubMed
49.
go back to reference Dai F, et al. The number and microlocalization of tumor-associated immune cells are associated with patient's survival time in non-small cell lung cancer. BMC Cancer. 2010;10:220.CrossRefPubMedPubMedCentral Dai F, et al. The number and microlocalization of tumor-associated immune cells are associated with patient's survival time in non-small cell lung cancer. BMC Cancer. 2010;10:220.CrossRefPubMedPubMedCentral
50.
go back to reference Sica A, et al. Macrophage polarization in tumour progression. Semin Cancer Biol. 2008;18(5):349–55.CrossRefPubMed Sica A, et al. Macrophage polarization in tumour progression. Semin Cancer Biol. 2008;18(5):349–55.CrossRefPubMed
51.
go back to reference Ohri CM, et al. Macrophages within NSCLC tumour islets are predominantly of a cytotoxic M1 phenotype associated with extended survival. Eur Respir J. 2009;33(1):118–26.CrossRefPubMed Ohri CM, et al. Macrophages within NSCLC tumour islets are predominantly of a cytotoxic M1 phenotype associated with extended survival. Eur Respir J. 2009;33(1):118–26.CrossRefPubMed
52.
go back to reference Mantovani A, Allavena P, Sica A. Tumour-associated macrophages as a prototypic type II polarised phagocyte population: role in tumour progression. Eur J Cancer. 2004;40(11):1660–7.CrossRefPubMed Mantovani A, Allavena P, Sica A. Tumour-associated macrophages as a prototypic type II polarised phagocyte population: role in tumour progression. Eur J Cancer. 2004;40(11):1660–7.CrossRefPubMed
53.
go back to reference Sica A, et al. Tumour-associated macrophages are a distinct M2 polarised population promoting tumour progression: potential targets of anti-cancer therapy. Eur J Cancer. 2006;42(6):717–27.CrossRefPubMed Sica A, et al. Tumour-associated macrophages are a distinct M2 polarised population promoting tumour progression: potential targets of anti-cancer therapy. Eur J Cancer. 2006;42(6):717–27.CrossRefPubMed
54.
go back to reference Edin S, et al. The distribution of macrophages with a M1 or M2 phenotype in relation to prognosis and the molecular characteristics of colorectal cancer. PLoS One. 2012;7(10):e47045.CrossRefPubMedPubMedCentral Edin S, et al. The distribution of macrophages with a M1 or M2 phenotype in relation to prognosis and the molecular characteristics of colorectal cancer. PLoS One. 2012;7(10):e47045.CrossRefPubMedPubMedCentral
55.
go back to reference Nagorsen D, et al. Tumor-infiltrating macrophages and dendritic cells in human colorectal cancer: relation to local regulatory T cells, systemic T-cell response against tumor-associated antigens and survival. J Transl Med. 2007;5:62.CrossRefPubMedPubMedCentral Nagorsen D, et al. Tumor-infiltrating macrophages and dendritic cells in human colorectal cancer: relation to local regulatory T cells, systemic T-cell response against tumor-associated antigens and survival. J Transl Med. 2007;5:62.CrossRefPubMedPubMedCentral
56.
go back to reference Tas F, et al. Serum levels of leptin and proinflammatory cytokines in advanced-stage non-small cell lung cancer. Med Oncol. 2005;22(4):353–8.CrossRefPubMed Tas F, et al. Serum levels of leptin and proinflammatory cytokines in advanced-stage non-small cell lung cancer. Med Oncol. 2005;22(4):353–8.CrossRefPubMed
57.
go back to reference Wei T, et al. Increased expression of immunosuppressive molecules on intratumoral and circulating regulatory T cells in non-small-cell lung cancer patients. Am J Cancer Res. 2015;5(7):2190–201.PubMedPubMedCentral Wei T, et al. Increased expression of immunosuppressive molecules on intratumoral and circulating regulatory T cells in non-small-cell lung cancer patients. Am J Cancer Res. 2015;5(7):2190–201.PubMedPubMedCentral
58.
go back to reference Martin F, et al. Cytokine levels (IL-6 and IFN-gamma), acute phase response and nutritional status as prognostic factors in lung cancer. Cytokine. 1999;11(1):80–6.CrossRefPubMed Martin F, et al. Cytokine levels (IL-6 and IFN-gamma), acute phase response and nutritional status as prognostic factors in lung cancer. Cytokine. 1999;11(1):80–6.CrossRefPubMed
60.
go back to reference Mantovani A, et al. The chemokine system in diverse forms of macrophage activation and polarization. Trends Immunol. 2004;25(12):677–86.CrossRefPubMed Mantovani A, et al. The chemokine system in diverse forms of macrophage activation and polarization. Trends Immunol. 2004;25(12):677–86.CrossRefPubMed
61.
go back to reference Guiducci C, et al. Redirecting in vivo elicited tumor infiltrating macrophages and dendritic cells towards tumor rejection. Cancer Res. 2005;65(8):3437–46.CrossRefPubMed Guiducci C, et al. Redirecting in vivo elicited tumor infiltrating macrophages and dendritic cells towards tumor rejection. Cancer Res. 2005;65(8):3437–46.CrossRefPubMed
62.
go back to reference Chanmee T, et al. Tumor-associated macrophages as major players in the tumor microenvironment. Cancers (Basel). 2014;6(3):1670–90.CrossRef Chanmee T, et al. Tumor-associated macrophages as major players in the tumor microenvironment. Cancers (Basel). 2014;6(3):1670–90.CrossRef
63.
go back to reference Ohtaki Y, et al. Stromal macrophage expressing CD204 is associated with tumor aggressiveness in lung adenocarcinoma. J Thorac Oncol. 2010;5(10):1507–15.CrossRefPubMed Ohtaki Y, et al. Stromal macrophage expressing CD204 is associated with tumor aggressiveness in lung adenocarcinoma. J Thorac Oncol. 2010;5(10):1507–15.CrossRefPubMed
64.
go back to reference Enewold L, et al. Serum concentrations of cytokines and lung cancer survival in African Americans and Caucasians. Cancer Epidemiol Biomark Prev. 2009;18(1):215–22.CrossRef Enewold L, et al. Serum concentrations of cytokines and lung cancer survival in African Americans and Caucasians. Cancer Epidemiol Biomark Prev. 2009;18(1):215–22.CrossRef
65.
go back to reference Derin D, et al. Serum levels of apoptosis biomarkers, survivin and TNF-alpha in nonsmall cell lung cancer. Lung Cancer. 2008;59(2):240–5.CrossRefPubMed Derin D, et al. Serum levels of apoptosis biomarkers, survivin and TNF-alpha in nonsmall cell lung cancer. Lung Cancer. 2008;59(2):240–5.CrossRefPubMed
66.
go back to reference Lu C, et al. Prognostic factors in resected stage I non-small-cell lung cancer: a multivariate analysis of six molecular markers. J Clin Oncol. 2004;22(22):4575–83.CrossRefPubMed Lu C, et al. Prognostic factors in resected stage I non-small-cell lung cancer: a multivariate analysis of six molecular markers. J Clin Oncol. 2004;22(22):4575–83.CrossRefPubMed
67.
go back to reference De Vita F, et al. Serum interleukin-10 levels as a prognostic factor in advanced non-small cell lung cancer patients. Chest. 2000;117(2):365–73.CrossRefPubMed De Vita F, et al. Serum interleukin-10 levels as a prognostic factor in advanced non-small cell lung cancer patients. Chest. 2000;117(2):365–73.CrossRefPubMed
Metadata
Title
Distribution of M1 and M2 macrophages in tumor islets and stroma in relation to prognosis of non-small cell lung cancer
Authors
Jurgita Jackute
Marius Zemaitis
Darius Pranys
Brigita Sitkauskiene
Skaidrius Miliauskas
Simona Vaitkiene
Raimundas Sakalauskas
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Immunology / Issue 1/2018
Electronic ISSN: 1471-2172
DOI
https://doi.org/10.1186/s12865-018-0241-4

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