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06.09.2024 | Research

CD68 positive and/or CD163 positive tumor-associated macrophages and PD-L1 expression in breast phyllodes tumor

verfasst von: Eunah Shin, Hye Min Kim, Ja Seung Koo

Erschienen in: Breast Cancer Research and Treatment

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Abstract

Introduction

PD-L1 expression and tumor-associated macrophage (TAM) status in phyllodes tumors (PT) have only been examined in a limited number of studies. This study aimed to investigate the expression of PD-L1 and TAM in breast PT and examine their implications.

Methods

Tissue microarrays were constructed from 181 PT samples, and immunohistochemistry for PD-L1 antibodies (SP142, SP263, and 22C3) and TAM markers (CD68 and CD163) were performed. The staining results were compared and analyzed with clinicopathological parameters.

Results

Of the 181 samples, 149 were benign, 27 were borderline, and five were malignant. The number of CD68- and/or CD163-positive TAMs increased with increasing PT grades (P < 0.001), and the number of CD68-positive TAMs was significantly positively correlated with that of CD163-positive TAMs (R = 0.704, P < 0.001). Some of the CD68- and/or CD163-positive cells exhibited positivity for actin staining, displaying hybrid characteristics that resemble both histiocytes and myofibroblasts. PD-L1 SP263 tumor cells and PD-L1 SP263 immune cells were the most expressed in malignant PTs (P < 0.001). The number of CD68- and/or CD163-positive TAMs increased when PD-L1 SP263 immune cells were expressed (P < 0.001). The number of CD68- and/or CD163-positive TAMs was positively correlated with PD-L1 22C3 immune cells (R = 0.299, P < 0.001 and R = 0.336, P < 0.001, respectively). Univariate analysis showed that PD-L1 SP263 immune cell expression (P = 0.016) was associated with shorter disease-free survival and that PD-L1 22C3 tumor cell expression (P < 0.001) was associated with shorter overall survival.

Conclusion

The number of CD68- and/or CD163-positive cells increases with increasing PT histological grade, and these cells exhibit hybrid characteristics, resembling both histiocyte and myofibroblasts.

Nur mit Berechtigung zugänglich

Anderson B, Lawton T, Lehman C, Moe R (2004) Phyllodes tumor. In: Morrow M, Osborne C (eds) Disease of the breast. Lippincott & Wilkins, Philadelphia, pp 991–1006

WHO Classification of Tumours Editorial Board (2019) World Heath Organization Classification of Tumors, 5th. IARC Press, Lyon

World Health Organization., International Agency for Research on Cancer (2020) WHO classification of tumours of breast, 5th edn. IARC Press, Lyon

Lenhard MS, Kahlert S, Himsl I et al (2008) Phyllodes tumour of the breast: clinical follow-up of 33 cases of this rare disease. Eur J Obstet Gynecol Reprod Biol 138(2):217–221. https://doi.org/10.1016/j.ejogrb.2007.08.002CrossRefPubMed

Karim RZ, Gerega SK, Yang YH et al (2009) Phyllodes tumours of the breast: a clinicopathological analysis of 65 cases from a single institution. Breast 18(3):165–170. https://doi.org/10.1016/j.breast.2009.03.001CrossRefPubMed

Tan PH, Thike AA, Tan WJ et al (2012) Predicting clinical behaviour of breast phyllodes tumours: a nomogram based on histological criteria and surgical margins. J Clin Pathol 65(1):69–76. https://doi.org/10.1136/jclinpath-2011-200368CrossRefPubMed

Dong H, Strome SE, Salomao DR et al (2002) Tumor-associated B7–H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med 8(8):793–800. https://doi.org/10.1038/nm730CrossRefPubMed

Brown JA, Dorfman DM, Ma FR et al (2003) Blockade of programmed death-1 ligands on dendritic cells enhances T cell activation and cytokine production. J Immunol 170(3):1257–1266CrossRefPubMed

Weber JS, Kudchadkar RR, Yu B et al (2013) Safety, efficacy, and biomarkers of nivolumab with vaccine in ipilimumab-refractory or -naive melanoma. J Clin Oncol 31(34):4311–4318. https://doi.org/10.1200/jco.2013.51.4802CrossRefPubMedPubMedCentral

10.

Tumeh PC, Harview CL, Yearley JH et al (2014) PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature 515(7528):568–571. https://doi.org/10.1038/nature13954CrossRefPubMedPubMedCentral

11.

Herbst RS, Soria JC, Kowanetz M et al (2014) Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature 515(7528):563–567. https://doi.org/10.1038/nature14011CrossRefPubMedPubMedCentral

12.

Powles T, Eder JP, Fine GD et al (2014) MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer. Nature 515(7528):558–562. https://doi.org/10.1038/nature13904CrossRefPubMed

13.

Chauhan A, Siegel L, Freese R et al (2021) Performance of Ventana SP263 PD-L1 assay in endobronchial ultrasound guided-fine-needle aspiration derived non-small-cell lung carcinoma samples. Diagn Cytopathol 49(3):355–362. https://doi.org/10.1002/dc.24654CrossRefPubMed

14.

Ai L, Xu A, Xu J (2020) Roles of PD-1/PD-L1 pathway: signaling, cancer, and beyond. Adv Exp Med Biol 1248:33–59. https://doi.org/10.1007/978-981-15-3266-5_3CrossRefPubMed

15.

Yi M, Zheng X, Niu M et al (2022) Combination strategies with PD-1/PD-L1 blockade: current advances and future directions. Mol Cancer 21(1):28. https://doi.org/10.1186/s12943-021-01489-2CrossRefPubMedPubMedCentral

16.

Martinez FO, Sica A, Mantovani A, Locati M (2008) Macrophage activation and polarization. Front Biosci 13:453–461CrossRefPubMed

17.

Cassetta L, Cassol E, Poli G (2011) Macrophage polarization in health and disease. Sci World J 11:2391–2402. https://doi.org/10.1100/2011/213962CrossRef

18.

Pollard JW (2004) Tumour-educated macrophages promote tumour progression and metastasis. Nat Rev Cancer 4(1):71–78. https://doi.org/10.1038/nrc1256CrossRefPubMed

19.

Mosser DM, Edwards JP (2008) Exploring the full spectrum of macrophage activation. Nat Rev Immunol 8(12):958–969. https://doi.org/10.1038/nri2448CrossRefPubMedPubMedCentral

20.

Li W, Wu F, Zhao S et al (2022) Correlation between PD-1/PD-L1 expression and polarization in tumor-associated macrophages: a key player in tumor immunotherapy. Cytokine Growth Factor Rev 67:49–57. https://doi.org/10.1016/j.cytogfr.2022.07.004CrossRefPubMed

21.

Pu Y, Ji Q (2022) Tumor-associated macrophages regulate PD-1/PD-L1 immunosuppression. Front Immunol 13:874589. https://doi.org/10.3389/fimmu.2022.874589CrossRefPubMedPubMedCentral

22.

Giunchi F, Gevaert T, Scarpelli M, Fiorentino M (2020) Status of Programmed Death Ligand 1 (PD-L1) by Immunohistochemistry and Scoring Algorithms. Curr Drug Targets 21(13):1286–1292. https://doi.org/10.2174/1389450121666200123124642CrossRefPubMed

23.

Cassidy M, Loftus B, Whelan A et al (1994) KP-1: not a specific marker Staining of 137 sarcomas, 48 lymphomas, 28 carcinomas, 7 malignant melanomas and 8 cystosarcoma phyllodes. Virchows Arch 424(6):635–640. https://doi.org/10.1007/bf00195778CrossRefPubMed

24.

Loftus B, Loh LC, Curran B et al (1991) Mac387: its non-specificity as a tumour marker or marker of histiocytes. Histopathology 19(3):251–255. https://doi.org/10.1111/j.1365-2559.1991.tb00030.xCrossRefPubMed

25.

Shabo I, Stål O, Olsson H et al (2008) Breast cancer expression of CD163, a macrophage scavenger receptor, is related to early distant recurrence and reduced patient survival. Int J Cancer 123(4):780–786. https://doi.org/10.1002/ijc.23527CrossRefPubMed

26.

Shabo I, Olsson H, Sun XF, Svanvik J (2009) Expression of the macrophage antigen CD163 in rectal cancer cells is associated with early local recurrence and reduced survival time. Int J Cancer 125(8):1826–1831. https://doi.org/10.1002/ijc.24506CrossRefPubMed

27.

Valadi H, Ekström K, Bossios A et al (2007) Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 9(6):654–659. https://doi.org/10.1038/ncb1596CrossRefPubMed

28.

Shabo I, Svanvik J (2011) Expression of macrophage antigens by tumor cells. Adv Exp Med Biol 714:141–150. https://doi.org/10.1007/978-94-007-0782-5_7CrossRefPubMed

29.

Vignery A (2005) Macrophage fusion: the making of osteoclasts and giant cells. J Exp Med 202(3):337–340. https://doi.org/10.1084/jem.20051123CrossRefPubMedPubMedCentral

30.

Shabo I, Midtbö K, Andersson H et al (2015) Macrophage traits in cancer cells are induced by macrophage-cancer cell fusion and cannot be explained by cellular interaction. BMC Cancer 15:922. https://doi.org/10.1186/s12885-015-1935-0CrossRefPubMedPubMedCentral

31.

Ding J, Jin W, Chen C et al (2012) Tumor associated macrophage × cancer cell hybrids may acquire cancer stem cell properties in breast cancer. PLoS ONE 7(7):e41942. https://doi.org/10.1371/journal.pone.0041942CrossRefPubMedPubMedCentral

32.

Kim SI, Koo JS (2020) Expression of cancer stem cell markers in breast phyllodes tumor. Cancer Biomark 29(2):235–243. https://doi.org/10.3233/cbm-191276CrossRefPubMed

33.

Nie Y, Chen J, Huang D et al (2017) Tumor-associated macrophages promote malignant progression of breast phyllodes tumors by inducing myofibroblast differentiation. Cancer Res 77(13):3605–3618. https://doi.org/10.1158/0008-5472.Can-16-2709CrossRefPubMed

34.

Gatalica Z, Vranic S, Ghazalpour A et al (2016) Multiplatform molecular profiling identifies potentially targetable biomarkers in malignant phyllodes tumors of the breast. Oncotarget 7(2):1707–1716. https://doi.org/10.18632/oncotarget.6421CrossRefPubMed

35.

Witte HM, Gebauer N, Lappöhn D et al (2020) Prognostic impact of PD-L1 expression in malignant salivary gland tumors as assessed by established scoring criteria: Tumor Proportion Score (TPS), Combined Positivity Score (CPS), and immune cell (IC) infiltrate. Cancers (Basel). https://doi.org/10.3390/cancers12040873CrossRefPubMedPubMedCentral

36.

Huang S, Nong L, Liang L et al (2019) Comparison of PD-L1 detection assays and corresponding significance in evaluation of diffuse large B-cell lymphoma. Cancer Med 8(8):3831–3845. https://doi.org/10.1002/cam4.2316CrossRefPubMedPubMedCentral

37.

Sumitomo R, Hirai T, Fujita M et al (2019) PD-L1 expression on tumor-infiltrating immune cells is highly associated with M2 TAM and aggressive malignant potential in patients with resected non-small cell lung cancer. Lung Cancer 136:136–144. https://doi.org/10.1016/j.lungcan.2019.08.023CrossRefPubMed

38.

Guo H, Ding Q, Gong Y et al (2020) Comparison of three scoring methods using the FDA-approved 22C3 immunohistochemistry assay to evaluate PD-L1 expression in breast cancer and their association with clinicopathologic factors. Breast Cancer Res 22(1):69. https://doi.org/10.1186/s13058-020-01303-9CrossRefPubMedPubMedCentral

39.

Song P, Guo L, Li W et al (2019) Clinicopathologic correlation with expression of PD-L1 on both tumor cells and tumor-infiltrating immune cells in patients with non-small cell lung cancer. J Immunother 42(1):23–28. https://doi.org/10.1097/cji.0000000000000249CrossRefPubMed

40.

Zhang J, Song L, Zhu H et al (2022) Prognostic value of programmed cell death ligand-1 expression in patients with bladder urothelial carcinoma undergoing radical cystectomy: A meta-analysis. Front Immunol 13:986911. https://doi.org/10.3389/fimmu.2022.986911CrossRefPubMedPubMedCentral

41.

Cheng N, Bai X, Shu Y et al (2021) Targeting tumor-associated macrophages as an antitumor strategy. Biochem Pharmacol 183:114354. https://doi.org/10.1016/j.bcp.2020.114354CrossRefPubMed

42.

Zhang SY, Song XY, Li Y et al (2020) Tumor-associated macrophages: a promising target for a cancer immunotherapeutic strategy. Pharmacol Res 161:105111. https://doi.org/10.1016/j.phrs.2020.105111CrossRefPubMed

43.

Chen Y, Jin H, Song Y et al (2021) Targeting tumor-associated macrophages: a potential treatment for solid tumors. J Cell Physiol 236(5):3445–3465. https://doi.org/10.1002/jcp.30139CrossRefPubMed

44.

Nie Y, Huang H, Guo M et al (2019) Breast phyllodes tumors recruit and repolarize tumor-associated macrophages via secreting CCL5 to promote malignant progression, which can be inhibited by ccr5 inhibition therapy. Clin Cancer Res 25(13):3873–3886. https://doi.org/10.1158/1078-0432.Ccr-18-3421CrossRefPubMed

Titel: CD68 positive and/or CD163 positive tumor-associated macrophages and PD-L1 expression in breast phyllodes tumor
verfasst von: Eunah Shin
Hye Min Kim
Ja Seung Koo
Publikationsdatum: 06.09.2024
Verlag: Springer US
Erschienen in: Breast Cancer Research and Treatment
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-024-07487-4

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