The Clinical Significance of CD169-Positive Lymph Node Macrophage in Patients with Breast Cancer

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2016 Nov 19

PMID 27861544

Citations 37

Authors

Takuya Shiota

Yuko Miyasato

Koji Ohnishi

Mutsuko Yamamoto-Ibusuki

Yutaka Yamamoto

Hirotaka Iwase

Motohiro Takeya

Yoshihiro Komohara

Affiliations

Soon will be listed here.

Abstract

The immune status of patients can impact on the clinical course of cancer. Lymph node (LN) macrophages play critical roles in anti-cancer immunity via the activation of cytotoxic T-lymphocytes (CTLs). In this study, the prognostic significance of CD169+ LN macrophages was examined in patients with breast cancer. For this purpose the number of CD169+ cells and their ratio relative to total macrophages (CD68+) in regional LNs (RLNs), as well as the number of CD8+ CTLs in tumor tissues, were investigated using immunohistochemistry of paraffin-embedded tissue samples from 146 patients with breast cancer. The association of these data with clinicopathological factors was then analyzed. The number of cells positive for the pan-macrophage marker CD68 remained relatively uniform, while the number of CD169+ cells varied across all cases. Moreover, a high density of CD169+ cells correlated with early clinical stage and no LN metastasis, while a higher CD169+ to CD68+ ratio was significantly associated with small tumor size and a low Ki-67+ rate. There was also a significant correlation between the number of CD8+ CTLs and that of CD169+ macrophages in high grade breast cancer cases with a Ki-67 index greater than 40%. However, neither the density nor the ratio of CD169+ cells, nor the density of CD8+ CTLs, were associated with relapse-free survival, distant relapse-free survival, or breast cancer-specific survival. These findings suggest that CD169+ macrophages in RLNs might be a useful marker for assessing clinical stage, including LN states, in patients with breast cancer.

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References

Naito Y, Saito K, Shiiba K, Ohuchi A, Saigenji K, Nagura H . CD8+ T cells infiltrated within cancer cell nests as a prognostic factor in human colorectal cancer. Cancer Res. 1998; 58(16):3491-4. View

Martinez-Pomares L, Gordon S . CD169+ macrophages at the crossroads of antigen presentation. Trends Immunol. 2011; 33(2):66-70. DOI: 10.1016/j.it.2011.11.001. View

Barral P, Polzella P, Bruckbauer A, van Rooijen N, Besra G, Cerundolo V . CD169(+) macrophages present lipid antigens to mediate early activation of iNKT cells in lymph nodes. Nat Immunol. 2010; 11(4):303-12. PMC: 2923071. DOI: 10.1038/ni.1853. View

Wu C, Rauch U, Korpos E, Song J, Loser K, Crocker P . Sialoadhesin-positive macrophages bind regulatory T cells, negatively controlling their expansion and autoimmune disease progression. J Immunol. 2009; 182(10):6508-16. PMC: 3733067. DOI: 10.4049/jimmunol.0804247. View

Xu C, Yamamoto-Ibusuki M, Yamamoto Y, Yamamoto S, Fujiwara S, Murakami K . High survivin mRNA expression is a predictor of poor prognosis in breast cancer: a comparative study at the mRNA and protein level. Breast Cancer. 2012; 21(4):482-90. DOI: 10.1007/s12282-012-0403-9. View

Asano K, Nabeyama A, Miyake Y, Qiu C, Kurita A, Tomura M . CD169-positive macrophages dominate antitumor immunity by crosspresenting dead cell-associated antigens. Immunity. 2011; 34(1):85-95. DOI: 10.1016/j.immuni.2010.12.011. View

Brown J, Wimberly H, Lannin D, Nixon C, Rimm D, Bossuyt V . Multiplexed quantitative analysis of CD3, CD8, and CD20 predicts response to neoadjuvant chemotherapy in breast cancer. Clin Cancer Res. 2014; 20(23):5995-6005. PMC: 4252785. DOI: 10.1158/1078-0432.CCR-14-1622. View

Vicente Conesa M, Garcia-Martinez E, Gonzalez Billalabeitia E, Chaves Benito A, Garcia Garcia T, Vicente Garcia V . Predictive value of peripheral blood lymphocyte count in breast cancer patients treated with primary chemotherapy. Breast. 2011; 21(4):468-74. DOI: 10.1016/j.breast.2011.11.002. View

Anz D, Eiber S, Scholz C, Endres S, Kirchner T, Bourquin C . In breast cancer, a high ratio of tumour-infiltrating intraepithelial CD8+ to FoxP3+ cells is characteristic for the medullary subtype. Histopathology. 2011; 59(5):965-74. DOI: 10.1111/j.1365-2559.2011.04040.x. View

10.

Darby S, McGale P, Correa C, Taylor C, Arriagada R, Clarke M . Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10,801 women in 17 randomised trials. Lancet. 2011; 378(9804):1707-16. PMC: 3254252. DOI: 10.1016/S0140-6736(11)61629-2. View

11.

Gordon S, Martinez F . Alternative activation of macrophages: mechanism and functions. Immunity. 2010; 32(5):593-604. DOI: 10.1016/j.immuni.2010.05.007. View

12.

Takahashi R, Toh U, Iwakuma N, Takenaka M, Otsuka H, Furukawa M . Feasibility study of personalized peptide vaccination for metastatic recurrent triple-negative breast cancer patients. Breast Cancer Res. 2014; 16(4):R70. PMC: 4227005. DOI: 10.1186/bcr3685. View

13.

Yamamoto-Ibusuki M, Yamamoto Y, Yamamoto S, Fujiwara S, Fu P, Honda Y . Comparison of prognostic values between combined immunohistochemical score of estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, Ki-67 and the corresponding gene expression score in breast cancer. Mod Pathol. 2012; 26(1):79-86. DOI: 10.1038/modpathol.2012.151. View

14.

Sabatier R, Finetti P, Mamessier E, Adelaide J, Chaffanet M, Ali H . Prognostic and predictive value of PDL1 expression in breast cancer. Oncotarget. 2015; 6(7):5449-64. PMC: 4467160. DOI: 10.18632/oncotarget.3216. View

15.

Sharma P, Shen Y, Wen S, Yamada S, Jungbluth A, Gnjatic S . CD8 tumor-infiltrating lymphocytes are predictive of survival in muscle-invasive urothelial carcinoma. Proc Natl Acad Sci U S A. 2007; 104(10):3967-72. PMC: 1820692. DOI: 10.1073/pnas.0611618104. View

16.

Bernhard C, Ried C, Kochanek S, Brocker T . CD169+ macrophages are sufficient for priming of CTLs with specificities left out by cross-priming dendritic cells. Proc Natl Acad Sci U S A. 2015; 112(17):5461-6. PMC: 4418891. DOI: 10.1073/pnas.1423356112. View

17.

Liu Y, Komohara Y, Domenick N, Ohno M, Ikeura M, Hamilton R . Expression of antigen processing and presenting molecules in brain metastasis of breast cancer. Cancer Immunol Immunother. 2011; 61(6):789-801. PMC: 3365630. DOI: 10.1007/s00262-011-1137-9. View

18.

Kuka M, Iannacone M . The role of lymph node sinus macrophages in host defense. Ann N Y Acad Sci. 2014; 1319:38-46. DOI: 10.1111/nyas.12387. View

19.

Kohrt H, Nouri N, Nowels K, Johnson D, Holmes S, Lee P . Profile of immune cells in axillary lymph nodes predicts disease-free survival in breast cancer. PLoS Med. 2005; 2(9):e284. PMC: 1198041. DOI: 10.1371/journal.pmed.0020284. View

20.

Hartnell A, Steel J, Turley H, Jones M, Jackson D, Crocker P . Characterization of human sialoadhesin, a sialic acid binding receptor expressed by resident and inflammatory macrophage populations. Blood. 2001; 97(1):288-96. DOI: 10.1182/blood.v97.1.288. View