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

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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.

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References

  1. 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 67:435–446

    Article  PubMed  CAS  Google Scholar 

  2. 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

    Google Scholar 

  3. 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 111:173–177

    Article  PubMed  Google Scholar 

  4. 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 23:2220–2228

    Article  PubMed  PubMed Central  Google Scholar 

  5. 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 84:161–169

    Article  PubMed  CAS  Google Scholar 

  6. 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 129:1963–1969

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  7. 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 18:1493–1501

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

  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 190:3798–3805

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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 100:2160–2166

    Article  PubMed  CAS  Google Scholar 

  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 78:3255–3266

    Article  PubMed  CAS  Google Scholar 

  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 105:93–103

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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 104:1237–1244

    Article  PubMed  CAS  Google Scholar 

  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:e0166680

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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 22:393–402

    Article  PubMed  CAS  Google Scholar 

  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 50:185–194

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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–E4050

    Article  PubMed  CAS  Google Scholar 

  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:e111

    Article  CAS  Google Scholar 

  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 51:57–63

    Article  PubMed  CAS  Google Scholar 

  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 7:1755

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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 411:516–522

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

We thank Ms. Ikuko Miyakawa and Mr. Takenobu Nakagawa for their technical assistance. This work was supported by grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan (nos. 16H05162, 17H04060).

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Author notes

  1. Yoshihiro Komohara and Hiroto Takeya equally contributed to this work.

Authors and Affiliations

  1. Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, Honjo 1-1-1, Chuouku, Kumamoto, Kumamoto, 860-8556, Japan

    Yoshihiro Komohara, Hiroto Takeya, Nanako Wakigami, Natsuki Kusada & Motohiro Takeya

  2. Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kumamoto University, Honjo 1-1-1, Kumamoto, Kumamoto, 860-8556, Japan

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

  3. Department of Anatomic Pathology, Graduate School of Medical Science, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka, 812-8582, Japan

    Hirofumi Bekki, Shin Ishihara & Yoshinao Oda

  4. Department of Orthopaedic Surgery, Graduate School of Medical Science, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka, 812-8582, Japan

    Hirofumi Bekki, Shin Ishihara & Yasuharu Nakashima

  5. Center for Metabolic Regulation of Healthy Aging, Kumamoto University, Honjo 1-1-1, Kumamoto, Kumamoto, 860-8556, Japan

    Yoshihiro Komohara

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  1. Yoshihiro Komohara
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  2. Hiroto Takeya
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  9. Yoshinao Oda
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Correspondence to Yoshihiro Komohara.

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Komohara, Y., Takeya, H., Wakigami, N. et al. Positive correlation between the density of macrophages and T-cells in undifferentiated sarcoma. Med Mol Morphol 52, 44–51 (2019). https://doi.org/10.1007/s00795-018-0201-3

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  • DOI: https://doi.org/10.1007/s00795-018-0201-3

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