Infiltration of PD-1-positive cells in combination with tumor site PD-L1 expression is a positive prognostic factor in cutaneous angiosarcoma
Open accessAbstract
Cutaneous angiosarcoma (CAS) is a malignant sarcoma with poor prognosis. Programmed cell death-1 (PD-1)/programmed cell death-1 ligand-1 (PD-L1) expression reflects antitumor immunity, and is associated with patient prognosis in various cancers. The purpose of this study is to investigate the relationship between PD-1/PD-L1 expression and CAS prognosis. CAS cases (n = 106) were immunohistochemically studied for PD-L1 and PD-1 expression, and the correlation with patient prognosis was analyzed. PD-L1 expression was assessed by flow cytometry on three CAS cell lines with or without IFNγ stimulation. A total of 30.2% of patients' samples were positive for PD-L1, and 17.9% showed a high infiltration of PD-1-positive cells. Univariate analysis showed a significant relationship between a high infiltration of PD-1-positive cells with tumor site PD-L1 expression and favorable survival in stage 1 patients (p = 0.014, log-rank test). Multivariable Cox-proportional hazard regression analysis also showed that patients with a high infiltration of PD-1-positive cells with tumor site PD-L1 expression were more likely to have favorable survival, after adjustment with possible confounders (hazard ratio (HR) = 0.38, p = 0.021, 95% confidence interval (CI) 0.16–0.86). Immunofluorescence staining of CAS samples revealed that PD-L1-positive cells were adjacent to PD-1-positive cells and/or tumor stroma with high IFNγ expression. In vitro stimulation with IFNγ increased PD-L1 expression in two out of three established CAS cell lines. Our results suggest that PD-1/PD-L1 expression is related to CAS progression, and the treatment with anti-PD-1 antibodies could be a new therapeutic option for CAS.
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Both cancer cells and tumor-infiltrating immune cells may express PD-L1 and upregulate it in response to IFN-γ.
“Both cancer cells and tumor-infiltrating immune cells (such as macrophages) may express PD-L1 and upregulate it in response to IFN-γ (60).”
From Anti-PD-1 and Anti-CTLA-4 Therapies in Cancer: Mechanisms of Action, Efficacy, and Limitations (2018) · cites this paper as [60]
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Self-citation
- Authors
- Honda, Y., Otsuka, A., Ono, S., Yamamoto, Y., Seidel, J. A., Morita, S., Hirata, M., Kataoka, T. R., Takenouchi, T., Fujii, K., Kanekura, T., Okubo, Y., Takahashi, K., Yanagi, T., Hoshina, D., Hata, H., Abe, R., Fujimura, T., Funakoshi, T., Yoshino, K., Masuzawa, M., Amoh, Y., Tanaka, R., Fujisawa, Y., Honda, T., & Kabashima, K.
- Affiliations
- Kyoto University (JP)
- Niigata Cancer Center Hospital (JP)
- Kagoshima University (JP)
- University of the Ryukyus (JP)
- Hokkaido University (JP)
- Niigata University (JP)
- Tohoku University (JP)
- Keio University (JP)
- Tokyo Metropolitan Komagome Hospital (JP)
- Kitasato University (JP)
- University of Tsukuba (JP)
- Corresponding author
- Otsuka, Atsushi
- Kabashima, Kenji
- ORCID
- Otsuka, Atsushi
- Ono, Sachiko
- Yamamoto, Yosuke
- Seidel, Judith A.
- Morita, Satoshi
- Hirata, Masahiro
- Kataoka, Tatsuki R.
- Takenouchi, Tatsuya
- Fujii, Kazuyasu
- Kanekura, Takuro
- Yanagi, Teruki
- Hoshina, Daichi
- Abe, Riichiro
- Fujimura, Taku
- Funakoshi, Takeru
- Masuzawa, Mamiko
- Amoh, Yasuyuki
- Tanaka, Ryota
- Fujisawa, Yasuhiro
- Honda, Tetsuya
- Kabashima, Kenji
- Venue
- OncoImmunology
- Publisher
- Informa UK Limited
- Published
- 2016-11-04
- Volume
- 6
- Issue
- 1
- Pages
- e1253657
- ISSN
- 2162-4011 (ISSN-L)
- 2162-402X
- PMC
- PMC5283640
- OpenAlex
- W2546582613
- Cited by
- 72
- References
- 36
- Citations by year
- 2026: 2 · 2025: 8 · 2024: 1 · 2023: 6 · 2022: 14 · 2021: 8 · 2020: 10 · 2019: 7 · 2018: 10 · 2017: 6
- FWCI
- 4.14
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- OncoImmunology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Agency for Medical Research and Development (16he0902003h0002, 16ek0410011h0003)
- Japan Society for the Promotion of Science (16he0902003h0002, 15H1155, 15K15417, 16ek0410011h0003, 15H05790, 15K08362)
- Japan Science and Technology Agency (16021031300)
- Precursory Research for Embryonic Science and Technology (16021031300)
- Topics
- Health Sciences › Medicine › Oncology › Vascular Tumors and Angiosarcomas
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Sarcoma Diagnosis and Treatment
- Keywords
- cutaneous angiosarcoma, PD-1, PD-L1, tumor-infiltrating lymphocytes, prognostic factors, survival, interferon-gamma, antitumor immunity, anti-PD-1 therapy, tumor stroma
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