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01-03-2019 | Original Paper

Positive correlation between the density of macrophages and T-cells in undifferentiated sarcoma

Authors: Yoshihiro Komohara, Hiroto Takeya, Nanako Wakigami, Natsuki Kusada, Hirofumi Bekki, Shin Ishihara, Motohiro Takeya, Yasuharu Nakashima, Yoshinao Oda

Published in: Medical Molecular Morphology | Issue 1/2019

Abstract

Undifferentiated sarcoma (US) is a frequent soft tissue sarcoma. Although the 10-year survival rate is around 60%, advanced US is highly resistant to chemo/radiotherapy. The tumor microenvironment (TME) is closely associated with tumor progression. However, few studies of infiltrated immune cells in US have been published. In this study, we evaluated tumor-associated macrophages (TAMs) and CD8-positive cytotoxic T lymphocytes (CTLs) in 28 cases of US. Iba1, CD163, and CD204 were used as markers for TAMs. The density of CTLs was positively correlated with the density of TAMs. However, a negative correlation was seen between the density of CTLs and the percentage of CD204-positive TAMs. We found no significant association between the density of Iba1-/CD204-/CD8-positive cells and clinicopathological factors. No significant correlation between immune cell infiltration and clinical outcome was observed. Although we found no significant association between immune cells and clinicopathological factors, these findings may provide new insight into the characterization of immune cells in the TME of US.

Oda Y, Yamamoto H, Kohashi K, Yamada Y, Iura K, Ishii T, Maekawa A, Bekki H (2017) Soft tissue sarcomas: from a morphological to a molecular biological approach. Pathol Int 67:435–446CrossRefPubMed

Fletcher CDM, Chibon F, Mertens F (2013) Undifferentiated/unclassified sarcomas. In: Fletcher CDM, Bridge JA, Hogendoorn PCW, Mertens F (eds) WHO classification of tumours of soft tissue and bone. International Agency for Research on Cancer, Kyon, pp 236–238

Delisca GO, Mesko NW, Alamanda VK, Archer KR, Song Y, Halpern JL, Schwartz HS, Holt GE (2015) MFH and high-grade undifferentiated pleomorphic sarcoma-what’s in a name? J Surg Oncol 111:173–177CrossRefPubMed

Roland CL, May CD, Watson KL, Al Sannaa GA, Dineen SP, Feig R, Landers S, Ingram DR, Wang WL, Guadagnolo BA, Feig B, Hunt KK, Cormier JN, Lazar AJ, Torres KE (2016) Analysis of clinical and molecular factors impacting oncologic outcomes in undifferentiated pleomorphic sarcoma. Ann Surg Oncol 23:2220–2228CrossRefPubMedPubMedCentral

Bekki H, Kohashi K, Yamada Y, Iura K, Ishii T, Maekawa A, Otsuka H, Yamamoto H, Hakozaki M, Nabeshima K, Iwamoto Y, Oda Y (2017) Phosphorylation of STAT3 in undifferentiated pleomorphic sarcoma is correlated with a favorable prognosis. Pathobiology 84:161–169CrossRefPubMed

Mahmood ST, Agresta S, Vigil CE, Zhao X, Han G, D’Amato G, Calitri CE, Dean M, Garrett C, Schell MJ, Antonia S, Chiappori A (2011) Phase II study of sunitinib malate, a multitargeted tyrosine kinase inhibitor in patients with relapsed or refractory soft tissue sarcomas. Focus on three prevalent histologies: leiomyosarcoma, liposarcoma and malignant fibrous histiocytoma. Int J Cancer 129:1963–1969CrossRefPubMedPubMedCentral

Tawbi HA, Burgess M, Bolejack V, Van Tine BA, Schuetze SM, Hu J, D’Angelo S, Attia S, Riedel RF, Priebat DA, Movva S, Davis LE, Okuno SH, Reed DR, Crowley J, Butterfield LH, Salazar R, Rodriguez-Canales J, Lazar AJ, Wistuba II, Baker LH, Maki RG, Reinke D, Patel S (2017) Pembrolizumab in advanced soft-tissue sarcoma and bone sarcoma (SARC028): a multicentre, two-cohort, single-arm, open-label, phase 2 trial. Lancet Oncol 18:1493–1501CrossRefPubMed

Kitamura T, Qian BZ, Pollard JW (2015) Immune cell promotion of metastasis. Nat Rev Immunol 15:73–86CrossRefPubMedPubMedCentral

Engblom C, Pfirschke C, Pittet MJ (2016) The role of myeloid cells in cancer therapies. Nat Rev Cancer 16:447–462CrossRefPubMed

10.

Mantovani A, Marchesi F, Malesci A, Laghi L, Allavena P (2017) Tumour-associated macrophages as treatment targets in oncology. Nat Rev Clin Oncol 14:399–416CrossRefPubMedPubMedCentral

11.

Komohara Y, Jinushi M, Takeya M (2014) Clinical significance of macrophage heterogeneity in human malignant tumors. Cancer Sci 105:1–8CrossRefPubMed

12.

Komohara Y, Takeya M (2017) CAFs and TAMs: maestros of the tumour microenvironment. J Pathol 241:313–315CrossRefPubMed

13.

Lewis CE, Harney AS, Pollard JW (2016) The multifaceted role of perivascular macrophages in tumors. Cancer Cell 30:18–25CrossRefPubMedPubMedCentral

14.

Takeya M, Komohara Y (2016) Role of tumor-associated macrophages in human malignancies: friend or foe? Pathol Int 66:491–505CrossRefPubMed

15.

Neyen C, Plüddemann A, Mukhopadhyay S, Maniati E, Bossard M, Gordon S, Hagemann T (2013) Macrophage scavenger receptor a promotes tumor progression in murine models of ovarian and pancreatic cancer. J Immunol 190:3798–3805CrossRefPubMedPubMedCentral

16.

Komohara Y, Takemura K, Lei XF, Sakashita N, Harada M, Suzuki H, Kodama T, Takeya M (2009) Delayed growth of EL4 lymphoma in SR-A-deficient mice is due to upregulation of nitric oxide and interferon-gamma production by tumor-associated macrophages. Cancer Sci 100:2160–2166CrossRefPubMed

17.

Shiraishi D, Fujiwara Y, Horlad H, Saito Y, Iriki T, Tsuboki J, Cheng P, Nakagata N, Mizuta H, Bekki H, Nakashima Y, Oda Y, Takeya M, Komohara Y (2018) CD163 is required for protumoral activation of macrophages in human and murine sarcoma. Cancer Res 78:3255–3266CrossRefPubMed

18.

Gooden MJ, de Bock GH, Leffers N, Daemen T, Nijman HW (2011) The prognostic influence of tumour-infiltrating lymphocytes in cancer: a systematic review with meta-analysis. Br J Cancer 105:93–103CrossRefPubMedPubMedCentral

19.

Ohnishi K, Komohara Y, Saito Y, Miyamoto Y, Watanabe M, Baba H, Takeya M (2013) CD169-positive macrophages in regional lymph nodes are associated with a favorable prognosis in patients with colorectal carcinoma. Cancer Sci 104:1237–1244CrossRefPubMed

20.

Shiota T, Miyasato Y, Ohnishi K, Yamamoto-Ibusuki M, Yamamoto Y, Iwase H, Takeya M, Komohara Y (2016) The clinical significance of CD169-positive lymph node macrophage in patients with breast cancer. PLoS One 11:e0166680CrossRefPubMedPubMedCentral

21.

Clarke B, Tinker AV, Lee CH, Subramanian S, van de Rijn M, Turbin D, Kalloger S, Han G, Ceballos K, Cadungog MG, Huntsman DG, Coukos G, Gilks CB (2009) Intraepithelial T cells and prognosis in ovarian carcinoma: novel associations with stage, tumor type, and BRCA1 loss. Mod Pathol 22:393–402CrossRefPubMed

22.

Kurozumi S, Fujii T, Matsumoto H, Inoue K, Kurosumi M, Horiguchi J, Kuwano H (2017) Significance of evaluating tumor-infiltrating lymphocytes (TILs) and programmed cell death-ligand 1 (PD-L1) expression in breast cancer. Med Mol Morphol 50:185–194CrossRefPubMed

23.

Mills CD, Lenz LL, Harris RA (2016) A breakthrough: macrophage-directed cancer immunotherapy. Cancer Res 76:513–516CrossRefPubMedPubMedCentral

24.

Peranzoni E, Lemoine J, Vimeux L, Feuillet V, Barrin S, Kantari-Mimoun C, Bercovici N, Guérin M, Biton J, Ouakrim H, Régnier F, Lupo A, Alifano M, Damotte D, Donnadieu E (2018) Macrophages impede CD8 T cells from reaching tumor cells and limit the efficacy of anti-PD-1 treatment. Proc Natl Acad Sci USA 115:E4041–E4050CrossRefPubMed

25.

Fujiwara Y, Hizukuri Y, Yamashiro K, Makita N, Ohnishi K, Takeya M, Komohara Y, Hayashi Y (2016) Guanylate-binding protein 5 is a marker of interferon-γ-induced classically activated macrophages. Clin Transl Immunol 5:e111CrossRef

26.

Motoshima T, Miura Y, Wakigami N, Kusada N, Takano T, Inoshita N, Okaneya T, Sugiyama Y, Kamba T, Takeya M, Komohara Y (2018) Phenotypical change of tumor-associated macrophages in metastatic lesions of clear cell renal cell carcinoma. Med Mol Morphol 51:57–63CrossRefPubMed

27.

Kubota K, Moriyama M, Furukawa S, Rafiul HASM, Maruse Y, Jinno T, Tanaka A, Ohta M, Ishiguro N, Yamauchi M, Sakamoto M, Maehara T, Hayashida JN, Kawano S, Kiyoshima T, Nakamura S (2017) CD163+ CD204+ tumor-associated macrophages contribute to T cell regulation via interleukin-10 and PD-L1 production in oral squamous cell carcinoma. Sci Rep 7:1755CrossRefPubMedPubMedCentral

28.

Ohnishi K, Komohara Y, Fujiwara Y, Takemura K, Lei X, Nakagawa T, Sakashita N, Takeya M (2011) Suppression of TLR4-mediated inflammatory response by macrophage class A scavenger receptor (CD204). Biochem Biophys Res Commun 411:516–522CrossRefPubMed

Title: Positive correlation between the density of macrophages and T-cells in undifferentiated sarcoma
Authors: Yoshihiro Komohara
Hiroto Takeya
Nanako Wakigami
Natsuki Kusada
Hirofumi Bekki
Shin Ishihara
Motohiro Takeya
Yasuharu Nakashima
Yoshinao Oda
Publication date: 01-03-2019
Publisher: Springer Japan
Published in: Medical Molecular Morphology / Issue 1/2019
Print ISSN: 1860-1480
Electronic ISSN: 1860-1499
DOI: https://doi.org/10.1007/s00795-018-0201-3

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Positive correlation between the density of macrophages and T-cells in undifferentiated sarcoma

Abstract

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Abstract

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